Materiały źródłowe

• #1 Neuroblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448111/

  Neuroblastoma (NB) is the most frequently-occurring extracranial childhood tumor. It is classified as an embryonal neuroendocrine tumor, originating from neural crest progenitor cells. […] Risk factors for the acquisition of mutations in key genes leading to neuroblastoma have yet to be identified, although exposures during conception and pregnancy are a topic of investigation. Neuroblastoma can develop either sporadically or be transmitted in the germline. Most familial cases of neuroblastoma occur due to the inheritance of highly penetrant mutations in either the ALK or PHOX2B genes. […] Although up to 15% of sporadic cases of neuroblastoma arise from mutations in ALK, more common transforming mutations involve polymorphisms in BARD1 (2q35), LIN28B (6q16.3), or FLJ22536 (6p22.3). Cytogenetic aberrations can further include loss of chromosome 1p and 11q, copy number variation in 1q21, and gain of 17q. […] Notably, amplification of MYCN oncogene is seen in approximately 25% of patients and is associated with the poorest prognosis; 17q gain and 1p loss correlate with MYCN amplification.

• #2 Neuroblastoma | Causes, Symptoms, Diagnosis & Treatment

  https://www.cincinnatichildrens.org/health/n/neuroblastoma

  Neuroblastoma is the most common malignant (cancerous) extracranial solid tumor of childhood. It develops from the tissues that form the sympathetic nervous system, which is part of the nervous system that regulates involuntary body functions. […] Most neuroblastoma cells have abnormalities involving a particular chromosome (chromosome 1), and the more malignant tumors often have multiple copies of the oncogene MYCN in the tumor cells. Several other genetic abnormalities may also be present. […] Research currently being done to see if maternal exposure during pregnancy to toxic substances, environmental pollutants or radiation could be linked to development of the disease.

• #3 Neuroblastoma – UF Health

  https://ufhealth.org/conditions-and-treatments/neuroblastoma

  Neuroblastoma can occur in many areas of the body. It develops from the tissues that form the sympathetic nervous system. This is the part of the nervous system that controls body functions, such as heart rate and blood pressure, digestion, and levels of certain hormones. […] The cause of the tumor is not known. Experts believe that a defect in a gene may play a role. Half of tumors are present at birth. Neuroblastoma is most commonly diagnosed in children before the age of 5. Each year there are around 700 new cases in the United States. The disorder is slightly more common in boys.

• #4 Neuroblastoma – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/neuroblastoma/symptoms-causes/syc-20351017

  Neuroblastoma is a cancer that starts in cells called neuroblasts. Neuroblasts are immature nerve cells. They are found in several areas of the body. […] It’s not clear what causes neuroblastoma. This cancer starts in immature nerve cells called neuroblasts. Neuroblasts are found in several areas of the body. […] Neuroblastoma starts when neuroblasts develop changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] The cancer cells might form a mass called a tumor. The tumor can grow to invade and destroy healthy body tissue. In time, cancer cells can break away and spread to other parts of the body. When cancer spreads, it’s called metastatic cancer.

• #5 Causes of Neuroblastoma | Genetics of Neuroblastoma | American Cancer Society

  https://www.cancer.org/cancer/types/neuroblastoma/causes-risks-prevention/what-causes.html

  While there are a few known risk factors for neuroblastoma, the cause of most neuroblastomas is not known. […] Neuroblastomas can occur when normal fetal neuroblasts do not become mature cells, but instead continue to grow and divide. […] The reason some neuroblasts don’t mature is because they have changes in the DNA inside the cells. […] Cancers can be caused by DNA changes that create oncogenes, or that turn off tumor suppressor genes. […] Most often, neuroblastoma cells have chromosome changes (such as having too many or too few chromosomes, or missing part of a chromosome) that are likely to affect certain genes. […] Most neuroblastomas are the result of gene changes in neuroblasts that happen during the child’s development, sometimes even before birth. What causes these acquired gene changes is not known.

• #6

  https://www.acco.org/blog/childhood-neuroblastoma-cancer-causes-risk-factors-and-prevention/

  Neuroblastoma is caused by the abnormal development of immature nerve cells known as neuroblasts. As a fetus develops, most neuroblasts grow and eventually become mature nerve cells either before birth or in the first few months after birth. However, in some cases, neuroblasts do not develop correctly. Instead of becoming mature nerve cells, they continue to grow and divide. In some cases, these abnormal neuroblasts simply die off; however, in some rare cases, they develop into tumors or neuroblastoma. […] Unfortunately, scientists do not know why some neuroblasts develop and mature normally and others do not. Research is beginning to show a link between the development of neuroblastoma and abnormal changes to the DNA in the neuroblasts. These DNA mutations cause neuroblastoma cells to have an abnormal chromosomal structure (either too many or too few chromosomes). The abnormal chromosomal structure may cause the neuroblasts to develop into neuroblastoma; it may also impact how quickly the neuroblastoma grows and develops. In rare cases, this abnormal DNA is inherited from a parent. However, in most cases, it is the result of random gene changes that occurred at some point in the child’s development.

• #7 Causes of Neuroblastoma | Genetics of Neuroblastoma | American Cancer Society

  https://www.cancer.org/cancer/types/neuroblastoma/causes-risks-prevention/what-causes.html

  While there are a few known risk factors for neuroblastoma, the cause of most neuroblastomas is not known. […] Neuroblastomas can occur when normal fetal neuroblasts do not become mature cells, but instead continue to grow and divide. […] The reason some neuroblasts don’t mature is because they have changes in the DNA inside the cells. […] Cancers can be caused by DNA changes that create oncogenes, or that turn off tumor suppressor genes. […] Most often, neuroblastoma cells have chromosome changes (such as having too many or too few chromosomes, or missing part of a chromosome) that are likely to affect certain genes. […] Most neuroblastomas are the result of gene changes in neuroblasts that happen during the child’s development, sometimes even before birth. What causes these acquired gene changes is not known.

• #8 Neuroblastoma – Causes, Symptoms, Diagnosis & Treatment

  https://www.medindia.net/health/conditions/neuroblastoma.htm

  Neuroblastoma may sometimes be caused by a gene mutation passed from the parent to the child. In such cases the cancer occurs at a younger age and there is a higher probability of multiple tumors forming in the adrenal glands. […] The cause of most neuroblastomas (98-99%) is not known. Neuroblastomas develop when normal fetal neuroblasts fail to become mature nerve cells. Instead, they uncontrollably continue to grow and divide. […] In 1-2 % cases, neuroblastoma seems to occur because of inherited gene changes in the ALK oncogene and PHOX2B, a gene that normally helps nerve cells mature. […] Also, as of today there are no known lifestyle related or environmental causes of neuroblastomas. Hence no preventive action can be taken to prevent these cancers.

• #9 Neuroblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448111/

  Neuroblastoma (NB) is the most frequently-occurring extracranial childhood tumor. It is classified as an embryonal neuroendocrine tumor, originating from neural crest progenitor cells. […] Risk factors for the acquisition of mutations in key genes leading to neuroblastoma have yet to be identified, although exposures during conception and pregnancy are a topic of investigation. Neuroblastoma can develop either sporadically or be transmitted in the germline. Most familial cases of neuroblastoma occur due to the inheritance of highly penetrant mutations in either the ALK or PHOX2B genes. […] Although up to 15% of sporadic cases of neuroblastoma arise from mutations in ALK, more common transforming mutations involve polymorphisms in BARD1 (2q35), LIN28B (6q16.3), or FLJ22536 (6p22.3). Cytogenetic aberrations can further include loss of chromosome 1p and 11q, copy number variation in 1q21, and gain of 17q. […] Notably, amplification of MYCN oncogene is seen in approximately 25% of patients and is associated with the poorest prognosis; 17q gain and 1p loss correlate with MYCN amplification.

• #10 Neuroblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Neuroblastoma

  Neuroblastoma typically occurs due to a genetic mutation occurring in the first trimester of pregnancy. […] Rarely, it may be due to a mutation inherited. Environmental factors have not been found to be involved. […] The cause of neuroblastoma is not well understood. The great majority of cases are sporadic and nonfamilial. About 12% of cases run in families and have been linked to specific gene mutations. Familial neuroblastoma in some cases is caused by rare germline mutations in the anaplastic lymphoma kinase (ALK) gene. […] Germline mutations in the PHOX2B or KIF1B gene have been implicated in familial neuroblastoma, as well. Neuroblastoma is also a feature of neurofibromatosis type 1 and the Beckwith-Wiedemann syndrome. […] MYCN oncogene amplification within the tumor is a common finding in neuroblastoma. The degree of amplification shows a bimodal distribution: either 3- to 10-fold, or 100- to 300-fold. The presence of this mutation is highly correlated to advanced stages of disease.

• #11 Neuroblastoma: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/neuroblastoma/

  The KIF1B gene is a tumor suppressor gene located in the deleted region of chromosome 1, and mutations in this gene have been identified in some people with familial neuroblastoma, indicating it is involved in neuroblastoma development or progression. […] About 25 percent of people with neuroblastoma have extra copies of the MYCN gene, a phenomenon called gene amplification.

• #12 Neuroblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448111/

  Neuroblastoma (NB) is the most frequently-occurring extracranial childhood tumor. It is classified as an embryonal neuroendocrine tumor, originating from neural crest progenitor cells. […] Risk factors for the acquisition of mutations in key genes leading to neuroblastoma have yet to be identified, although exposures during conception and pregnancy are a topic of investigation. Neuroblastoma can develop either sporadically or be transmitted in the germline. Most familial cases of neuroblastoma occur due to the inheritance of highly penetrant mutations in either the ALK or PHOX2B genes. […] Although up to 15% of sporadic cases of neuroblastoma arise from mutations in ALK, more common transforming mutations involve polymorphisms in BARD1 (2q35), LIN28B (6q16.3), or FLJ22536 (6p22.3). Cytogenetic aberrations can further include loss of chromosome 1p and 11q, copy number variation in 1q21, and gain of 17q. […] Notably, amplification of MYCN oncogene is seen in approximately 25% of patients and is associated with the poorest prognosis; 17q gain and 1p loss correlate with MYCN amplification.

• #13 Cell death-based treatment of neuroblastoma | Cell Death & Disease

  https://www.nature.com/articles/s41419-017-0060-1

  Therefore, investigation of the MYCN gene amplification is considered to be a mandatory step for treatment specification. […] Changes in the ALK gene are identified as being responsible for ~50% of familial and ~1% of all NBs. […] The central role of the ALK in NB development makes it a possible target for NB treatment. […] Amplifications of the MYCN gene are known to be responsible for increased tumor growth, proliferation, and NB development. […] Therefore, downregulation of MYCN is one possible approach to induce apoptosis, decrease NB proliferation, and/or induce neuronal differentiation. […] Overexpression and amplifications of LIN28B are very common in NB cells and can in turn lead to high MYCN expression. […] Chromosomal copy number alterations are also represented in almost all NBs, for example, more than 50% have gain of 17q and 30% have loss of 1p36 and/or 11q.

• #14 Neuroblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448111/

  Neuroblastoma (NB) is the most frequently-occurring extracranial childhood tumor. It is classified as an embryonal neuroendocrine tumor, originating from neural crest progenitor cells. […] Risk factors for the acquisition of mutations in key genes leading to neuroblastoma have yet to be identified, although exposures during conception and pregnancy are a topic of investigation. Neuroblastoma can develop either sporadically or be transmitted in the germline. Most familial cases of neuroblastoma occur due to the inheritance of highly penetrant mutations in either the ALK or PHOX2B genes. […] Although up to 15% of sporadic cases of neuroblastoma arise from mutations in ALK, more common transforming mutations involve polymorphisms in BARD1 (2q35), LIN28B (6q16.3), or FLJ22536 (6p22.3). Cytogenetic aberrations can further include loss of chromosome 1p and 11q, copy number variation in 1q21, and gain of 17q. […] Notably, amplification of MYCN oncogene is seen in approximately 25% of patients and is associated with the poorest prognosis; 17q gain and 1p loss correlate with MYCN amplification.

• #15 Neuroblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448111/

  Neuroblastoma (NB) is the most frequently-occurring extracranial childhood tumor. It is classified as an embryonal neuroendocrine tumor, originating from neural crest progenitor cells. […] Risk factors for the acquisition of mutations in key genes leading to neuroblastoma have yet to be identified, although exposures during conception and pregnancy are a topic of investigation. Neuroblastoma can develop either sporadically or be transmitted in the germline. Most familial cases of neuroblastoma occur due to the inheritance of highly penetrant mutations in either the ALK or PHOX2B genes. […] Although up to 15% of sporadic cases of neuroblastoma arise from mutations in ALK, more common transforming mutations involve polymorphisms in BARD1 (2q35), LIN28B (6q16.3), or FLJ22536 (6p22.3). Cytogenetic aberrations can further include loss of chromosome 1p and 11q, copy number variation in 1q21, and gain of 17q. […] Notably, amplification of MYCN oncogene is seen in approximately 25% of patients and is associated with the poorest prognosis; 17q gain and 1p loss correlate with MYCN amplification.

• #16 Neuroblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448111/

  Neuroblastoma (NB) is the most frequently-occurring extracranial childhood tumor. It is classified as an embryonal neuroendocrine tumor, originating from neural crest progenitor cells. […] Risk factors for the acquisition of mutations in key genes leading to neuroblastoma have yet to be identified, although exposures during conception and pregnancy are a topic of investigation. Neuroblastoma can develop either sporadically or be transmitted in the germline. Most familial cases of neuroblastoma occur due to the inheritance of highly penetrant mutations in either the ALK or PHOX2B genes. […] Although up to 15% of sporadic cases of neuroblastoma arise from mutations in ALK, more common transforming mutations involve polymorphisms in BARD1 (2q35), LIN28B (6q16.3), or FLJ22536 (6p22.3). Cytogenetic aberrations can further include loss of chromosome 1p and 11q, copy number variation in 1q21, and gain of 17q. […] Notably, amplification of MYCN oncogene is seen in approximately 25% of patients and is associated with the poorest prognosis; 17q gain and 1p loss correlate with MYCN amplification.

• #17 Pediatric Neuroblastoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/988284-overview

  The challenge for drug development in neuroblastoma is to identify upfront high-risk cases that may benefit from ALK-directed therapy. […] Genome-wide association studies (GWAS) have been used to discover numerous genetic variations associated with neuroblastoma. […] Variations in LMO1, BARD1, and FLJ22536 have all been associated with aggressive forms of neuroblastoma. […] Genomic variations within DUSP12, DDX4, IL21RA, and HSD17B12 are associated with low-risk forms of neuroblastoma.

• #18 Neuroblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Neuroblastoma

  Duplicated segments of the LMO1 gene within neuroblastoma tumor cells have been shown to increase the risk of developing an aggressive form of the cancer. […] Several risk factors have been proposed and are the subject of ongoing research. Due to characteristic early onset, many studies have focused on parental factors around conception and during gestation. Factors investigated have included occupation (i.e. exposure to chemicals in specific industries), smoking, alcohol consumption, use of medicinal drugs during pregnancy, and birth factors; however, results have been inconclusive. […] Other studies have examined possible links with atopy and exposure to infection early in life, use of hormones and fertility drugs, and maternal use of hair dye.

• #19 Causes of Neuroblastoma | Genetics of Neuroblastoma | American Cancer Society

  https://www.cancer.org/cancer/types/neuroblastoma/causes-risks-prevention/what-causes.html

  In rare cases, neuroblastoma occurs as a result of gene changes inherited from a parent. […] It’s still not clear what causes many of the gene and chromosome changes that can lead to neuroblastoma. There are no known lifestyle-related or environmental causes of neuroblastomas, so it’s important to remember that there is nothing these children or their parents could have done to prevent these cancers.

• #20 Neuroblastoma > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/neuroblastoma

  Neuroblastomas are solid tumors that originate in developing nerve cells. (Changes to genes or chromosomes may cause developing nerve cells to multiply uncontrollably, leading to the formation of neuroblastomas.) […] Doctors dont yet know why most children develop neuroblastomas. About 1 to 2% of children may have a family history of neuroblastoma (known as familial or Inherited neuroblastoma). Genetic mutations in the ALK gene and PHOX2B gene are associated with inherited neuroblastomas. […] In families with cancer predisposition syndromes such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, and Noonan syndrome, children are at increased risk of developing neuroblastoma.

• #21 Neuroblastoma: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/neuroblastoma/

  Neuroblastoma occurs when immature nerve cells called neuroblasts become abnormal and multiply uncontrollably to form a tumor. […] Neuroblastoma and other cancers occur when a buildup of genetic mutations in critical genes—those that control cell growth and division (proliferation) or maturation (differentiation)—allow cells to grow and divide uncontrollably to form a tumor. […] In most cases, these genetic changes are acquired during a person’s lifetime and are called somatic mutations. […] When neuroblastoma is associated with somatic mutations, it is called sporadic neuroblastoma. […] It is thought that somatic mutations in at least two genes are required to cause sporadic neuroblastoma. […] Less commonly, gene mutations that increase the risk of developing cancer can be inherited from a parent.

• #22 Pediatric Neuroblastoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/988284-overview

  Neuroblastoma has been known to occur in the setting of other disorders that are linked to abnormal development of neural crest tissues, such as Hirschsprung disease or central congenital hypoventilation syndrome. […] Genome-wide analysis of neuroblastoma from these rare familial cases has identified a genetic defect involved in these cases. […] Cases of neuroblastoma that accompany other congenital abnormalities of the neural crest have been associated with a germline mutation in PHOX2B. This gene is a homeobox gene that acts as a regulator of autonomic nervous system development. […] In familial neuroblastoma cases that are not associated with other congenital disorders of neural crest development, ALK mutations have been identified in the germline. […] These mutations largely occur in the kinase domain causing activation of ALK signaling.

• #23 Neuroblastoma: Practice Essentials, Background, Relevant Anatomy

  https://emedicine.medscape.com/article/439263-overview

  About 1-2% of patients with neuroblastoma have a family history of the disease. Germline mutations associated with a genetic predisposition to neuroblastoma in these cases include the following: […] ALK mutation – Point mutations in the tyrosine kinase domain of the ALK gene are found in about 75% of familial neuroblastoma cases; somatic activating point mutations in ALK are also seen in about 9% of sporadic neuroblastoma cases. In addition, co-amplification of ALK and MYCN (the two genes are near each other on chromosome 2) occurs in a small proportion of neuroblastoma cases […] PHOX2B mutation – Germline loss-of-function PHOX2B mutations have been identified in rare patients with sporadic neuroblastoma and Ondine curse (congenital central hypoventilation) and/or Hirschsprung disease. Somatic PHOX2B mutations are found in about 2% of patients with sporadic neuroblastoma.

• #24 Hereditary Neuroblastoma | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/hereditary-neuroblastoma

  Most cases of neuroblastoma (NBL) occur sporadically, affecting individuals who have no family history of the disease. However, in 1-2 percent of cases, a susceptibility to develop neuroblastoma can be inherited from a parent. […] A predisposition to hereditary neuroblastoma is caused by alterations, also known as mutations, at specific areas within an individuals genetic information. […] Most hereditary neuroblastomas are caused by alterations in the ALK gene. […] ALK and PHOX2B mutations are believed to contribute to the development of neuroblastoma by increasing the proliferation of neural cells, which makes them more likely to become cancerous. […] Some individuals with hereditary neuroblastoma inherit an altered copy of either ALK or PHOX2B from a parent who carries the same genetic mutation.

• #25 Pediatric Neuroblastoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/988284-overview

  Neuroblastoma has been known to occur in the setting of other disorders that are linked to abnormal development of neural crest tissues, such as Hirschsprung disease or central congenital hypoventilation syndrome. […] Genome-wide analysis of neuroblastoma from these rare familial cases has identified a genetic defect involved in these cases. […] Cases of neuroblastoma that accompany other congenital abnormalities of the neural crest have been associated with a germline mutation in PHOX2B. This gene is a homeobox gene that acts as a regulator of autonomic nervous system development. […] In familial neuroblastoma cases that are not associated with other congenital disorders of neural crest development, ALK mutations have been identified in the germline. […] These mutations largely occur in the kinase domain causing activation of ALK signaling.

• #26 Neuroblastoma: Practice Essentials, Background, Relevant Anatomy

  https://emedicine.medscape.com/article/439263-overview

  About 1-2% of patients with neuroblastoma have a family history of the disease. Germline mutations associated with a genetic predisposition to neuroblastoma in these cases include the following: […] ALK mutation – Point mutations in the tyrosine kinase domain of the ALK gene are found in about 75% of familial neuroblastoma cases; somatic activating point mutations in ALK are also seen in about 9% of sporadic neuroblastoma cases. In addition, co-amplification of ALK and MYCN (the two genes are near each other on chromosome 2) occurs in a small proportion of neuroblastoma cases […] PHOX2B mutation – Germline loss-of-function PHOX2B mutations have been identified in rare patients with sporadic neuroblastoma and Ondine curse (congenital central hypoventilation) and/or Hirschsprung disease. Somatic PHOX2B mutations are found in about 2% of patients with sporadic neuroblastoma.

• #27 Neuroblastoma: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/neuroblastoma/

  The KIF1B gene is a tumor suppressor gene located in the deleted region of chromosome 1, and mutations in this gene have been identified in some people with familial neuroblastoma, indicating it is involved in neuroblastoma development or progression. […] About 25 percent of people with neuroblastoma have extra copies of the MYCN gene, a phenomenon called gene amplification.

• #28 Neuroblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Neuroblastoma

  Neuroblastoma typically occurs due to a genetic mutation occurring in the first trimester of pregnancy. […] Rarely, it may be due to a mutation inherited. Environmental factors have not been found to be involved. […] The cause of neuroblastoma is not well understood. The great majority of cases are sporadic and nonfamilial. About 12% of cases run in families and have been linked to specific gene mutations. Familial neuroblastoma in some cases is caused by rare germline mutations in the anaplastic lymphoma kinase (ALK) gene. […] Germline mutations in the PHOX2B or KIF1B gene have been implicated in familial neuroblastoma, as well. Neuroblastoma is also a feature of neurofibromatosis type 1 and the Beckwith-Wiedemann syndrome. […] MYCN oncogene amplification within the tumor is a common finding in neuroblastoma. The degree of amplification shows a bimodal distribution: either 3- to 10-fold, or 100- to 300-fold. The presence of this mutation is highly correlated to advanced stages of disease.

• #29 Hereditary Neuroblastoma | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/hereditary-neuroblastoma

  Individuals who carry an ALK or PHOX2B gene mutation but never acquire these other genetic alterations may be less likely to develop neuroblastoma. […] Individuals with an altered ALK or PHOX2B gene are at increased risk to develop neuroblastoma. […] Currently, it is believed that approximately 50-60 percent of individuals with an ALK alteration will develop neuroblastoma.

• #30 Pediatric Neuroblastoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/988284-overview

  The cause of neuroblastoma is unknown, and no specific environmental exposure or risk factors have been identified. […] Because of young age of onset with this disease, investigators have focused on events before conception and during gestation. […] According to SEER data, factors investigated for which evidence is limited or inconsistent include medications, hormones, birth characteristics, congenital anomalies, previous spontaneous abortion or fetal death, alcohol or tobacco use, and paternal occupational exposures. […] The vast majority of neuroblastoma arises sporadically without family history of the disease. However, 1-2% of newly diagnosed cases do have a family history of neuroblastoma. Patients with familial neuroblastoma often present at earlier age or with several distinct primary tumors.

• #31

  https://www.beaumont.org/conditions/neuroblastoma

  The only risk factor that has been established for neuroblastoma is heredity, although the vast majority of neuroblastomas are not inherited. […] Recent research indicates that certain genetic variations double the risk of this disease. […] Also, having this particular variation increases the chance that a child will develop a more aggressive form of the disease. […] The average age at diagnosis in genetically linked cases is younger than those cases that are not inherited. […] Cancer that presents in several different areas of the body at once is a sign that it may be a genetically inherited cancer.

• #32 Neuroblastoma > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/neuroblastoma

  Neuroblastomas are solid tumors that originate in developing nerve cells. (Changes to genes or chromosomes may cause developing nerve cells to multiply uncontrollably, leading to the formation of neuroblastomas.) […] Doctors dont yet know why most children develop neuroblastomas. About 1 to 2% of children may have a family history of neuroblastoma (known as familial or Inherited neuroblastoma). Genetic mutations in the ALK gene and PHOX2B gene are associated with inherited neuroblastomas. […] In families with cancer predisposition syndromes such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, and Noonan syndrome, children are at increased risk of developing neuroblastoma.

• #33 Risk factors for neuroblastoma | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/neuroblastoma/risks

  Children with neurofibromatosis type 1 have a higher risk of developing certain cancers, including neuroblastoma. […] Children with Beckwith-Wiedemann syndrome have a higher risk of developing certain cancers, including neuroblastoma. […] Li-Fraumeni syndrome greatly increases a childs risk of developing several types of cancer, including neuroblastoma. […] Children with Costello syndrome have a higher risk of developing certain cancers, including neuroblastoma.

• #34 Neuroblastoma | Conditions | UCSF Benioff Children’s Hospitals

  https://www.ucsfbenioffchildrens.org/conditions/neuroblastoma

  Neuroblastoma is always linked to a genetic change that causes neuroblastoma cells to divide and grow uncontrollably. In most cases, the gene mutation is spontaneous, occurring for reasons unknown. In a small number of cases, the condition is caused by an inherited gene mutation. […] Certain genetic conditions can increase a child’s risk of developing neuroblastoma. These include: Costello syndrome, Noonan syndrome, Neurofibromatosis type 1, Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Pheochromocytoma/paraganglioma syndromes, ROHAAD syndromes (rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysfunction).

• #35 Neuroblastoma Risk Factors | American Cancer Society | American Cancer Society

  https://www.cancer.org/cancer/types/neuroblastoma/causes-risks-prevention/risk-factors.html

  Neuroblastoma is most common in infants and very young children. It is very rare in people over the age of 10 years. […] Most neuroblastomas do not seem to run in families. But in about 1% to 2% of cases, children with neuroblastoma have a family history of it. […] Some studies have shown that children with certain birth defects might have an increased risk of developing neuroblastoma. Some of the link between birth defects and neuroblastoma might be related to changes in genes that happen during fetal development. […] Changes in genes during fetal development might also increase the risk of some kinds of childhood cancers, like neuroblastoma.

• #36 Neuroblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Neuroblastoma

  Duplicated segments of the LMO1 gene within neuroblastoma tumor cells have been shown to increase the risk of developing an aggressive form of the cancer. […] Several risk factors have been proposed and are the subject of ongoing research. Due to characteristic early onset, many studies have focused on parental factors around conception and during gestation. Factors investigated have included occupation (i.e. exposure to chemicals in specific industries), smoking, alcohol consumption, use of medicinal drugs during pregnancy, and birth factors; however, results have been inconclusive. […] Other studies have examined possible links with atopy and exposure to infection early in life, use of hormones and fertility drugs, and maternal use of hair dye.

• #37 Neuroblastoma Risk Factors | American Cancer Society | American Cancer Society

  https://www.cancer.org/cancer/types/neuroblastoma/causes-risks-prevention/risk-factors.html

  Neuroblastoma is most common in infants and very young children. It is very rare in people over the age of 10 years. […] Most neuroblastomas do not seem to run in families. But in about 1% to 2% of cases, children with neuroblastoma have a family history of it. […] Some studies have shown that children with certain birth defects might have an increased risk of developing neuroblastoma. Some of the link between birth defects and neuroblastoma might be related to changes in genes that happen during fetal development. […] Changes in genes during fetal development might also increase the risk of some kinds of childhood cancers, like neuroblastoma.

• #38 Neuroblastoma: Causes, symptoms & treatment | Live Science

  https://www.livescience.com/neuroblastoma.html

  Neuroblastoma is a rare type of cancerous tumor that’s most commonly diagnosed in infants and children under age 5. It is extremely rare in people over age 10. […] About 800 new cases of neuroblastoma are diagnosed each year in the United States, according to the American Cancer Society. It accounts for about 6% of all childhood cancers, and it’s the most common tumor in infants. […] The cancer begins in the early forms of nerve cells called neuroblasts. As a fetus develops, most neuroblasts grow and eventually become mature nerve cells, either before birth or in a baby’s first few months of life, according to the American Childhood Cancer Organization. But in neuroblastoma, the neuroblasts don’t develop correctly. Instead of becoming mature nerve cells, they continue to grow and divide.

• #39 Who gets neuroblastoma? | Alex’s Lemonade Stand Foundation for Childhood Cancer

  https://www.alexslemonade.org/childhood-cancer/guides/childhood-cancer/chapter-4-neuroblastoma/who-gets-neuroblastoma

  Neuroblastoma is the second most common solid tumor in children (brain tumors are the most common). Each year more than 800 children are diagnosed with neuroblastoma in North America. Boys are diagnosed more often than girls, and there is a slightly higher incidence among White children than among Black children, although Black children are more likely to be diagnosed with high-risk disease. More than half of all neuroblastomas are diagnosed in children ages 2 years or younger, 89 percent are diagnosed before age 5, and 98 percent are diagnosed by age 10. Neuroblastoma is the most common cancer diagnosed in the first year of life. […] For reasons that are not understood, sympathetic nerve cells that are at the very beginning of their growth cycle sometimes begin to divide rapidly and form tumors, instead of maturing normally.

• #40 Neuroblastoma Risk Factors | American Cancer Society | American Cancer Society

  https://www.cancer.org/cancer/types/neuroblastoma/causes-risks-prevention/risk-factors.html

  Neuroblastoma is most common in infants and very young children. It is very rare in people over the age of 10 years. […] Most neuroblastomas do not seem to run in families. But in about 1% to 2% of cases, children with neuroblastoma have a family history of it. […] Some studies have shown that children with certain birth defects might have an increased risk of developing neuroblastoma. Some of the link between birth defects and neuroblastoma might be related to changes in genes that happen during fetal development. […] Changes in genes during fetal development might also increase the risk of some kinds of childhood cancers, like neuroblastoma.

• #41 Prenatal and perinatal risk factors for neuroblastoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6276802/

  Neuroblastoma is a rare embryonal tumor of childhood for which risk factors are not well known. […] Increased risks were associated with maternal anemia during pregnancy (odds ratio (OR)=2.95, 95% confidence interval (CI): 1.53, 5.69), neonatal respiratory distress (OR=3.61, 95% CI: 1.41, 9.24), and low (below or equal to 7) 1-minute Apgar score (OR=2.23, 95% CI:1.41, 3.52). […] The etiology of neuroblastoma overall or within prognostic subtypes is poorly understood. […] About 40% of cases are diagnosed prior to age 1, and over 80% before age 4. […] Some studies have reported associations with gestational exposure to maternal medications, parental occupational exposures, maternal reproductive history and pregnancy course, delivery method and anesthesia, low or high birthweight, and congenital abnormalities, but the findings have been inconsistent.

• #42 Neuroblastoma – EyeWiki

  https://eyewiki.org/Neuroblastoma

  Neuroblastomas can occur both sporadically and through an inherited mutation. Germline mutations in the anaplastic lymphoma kinase gene (ALK), aberrations in Phox2b and deletions of chromosome arms 1p and 11q are risk factors for familial neuroblastomas. Amplification of the MYCN oncogene is a common finding, and shows a bimodal distribution of amplification: either 3- to 10-fold, or 100- to 300-fold. This amplification has been linked to more aggressive forms of neuroblastoma. Duplicated segments of the LMO1 gene have also been identified as a risk factor for developing an aggressive form of neuroblastoma. […] Since neuroblastoma is so prevalent among infants, there have been numerous retrospective case report cohorts investigating pre- and perinatal risk factors. Risk factors were stratified based on younger and older infants. Among younger infants, high birth weight, heavier maternal gestational weight gain, maternal hypertension, older maternal age, ultrasound, and respiratory distress are suggested to increase the risk of neuroblastoma. Among older infants, low birth weight was associated with increased risk while greater maternal gestational weight gain was protective. In the oldest age group, first born status, primary cesarean delivery, prolonged labor and premature rupture of the membranes were associated with increased risk. Maternal ingestion of diuretics and other antihypertensives is linked with infant neuroblastoma, and is linked less strongly with maternal ingestion of vitamin, folate and iron supplementation. No associations were seen with pain relievers, antinauseants or cold medications. Additionally, low (below or equal to 7) 1-min Apgar scores, maternal anemia during pregnancy, maternal history of one fetal loss, and use of temporary hair dye in the month before and/or during pregnancy have been associated with an increased risk of neuroblastoma. […] There are no known separate risk factors for orbital metastasis from neuroblastomas.

• #43 Prenatal and perinatal risk factors for neuroblastoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6276802/

  This population-based record-linkage study in Sweden found that cases of neuroblastoma diagnosed before 1 year of age were associated with a constellation of prenatal and perinatal factors including maternal anemia, hemolysis, low 1-minute Apgar scores and neonatal respiratory distress. […] These perinatal conditions were not associated with the typically more aggressive and treatment-resistant cases of neuroblastoma diagnosed after 1 year of age.

• #44 Causes of Neuroblastoma | Genetics of Neuroblastoma | American Cancer Society

  https://www.cancer.org/cancer/types/neuroblastoma/causes-risks-prevention/what-causes.html

  In rare cases, neuroblastoma occurs as a result of gene changes inherited from a parent. […] It’s still not clear what causes many of the gene and chromosome changes that can lead to neuroblastoma. There are no known lifestyle-related or environmental causes of neuroblastomas, so it’s important to remember that there is nothing these children or their parents could have done to prevent these cancers.

• #45 Neuroblastoma – Causes, Symptoms, Diagnosis & Treatment

  https://www.medindia.net/health/conditions/neuroblastoma.htm

  Neuroblastoma may sometimes be caused by a gene mutation passed from the parent to the child. In such cases the cancer occurs at a younger age and there is a higher probability of multiple tumors forming in the adrenal glands. […] The cause of most neuroblastomas (98-99%) is not known. Neuroblastomas develop when normal fetal neuroblasts fail to become mature nerve cells. Instead, they uncontrollably continue to grow and divide. […] In 1-2 % cases, neuroblastoma seems to occur because of inherited gene changes in the ALK oncogene and PHOX2B, a gene that normally helps nerve cells mature. […] Also, as of today there are no known lifestyle related or environmental causes of neuroblastomas. Hence no preventive action can be taken to prevent these cancers.

• #46 Who gets neuroblastoma? | Alex’s Lemonade Stand Foundation for Childhood Cancer

  https://www.alexslemonade.org/childhood-cancer/guides/childhood-cancer/chapter-4-neuroblastoma/who-gets-neuroblastoma

  Most neuroblastoma tumors arise spontaneously, and there is no known environmental cause. Approximately 1 to 2 percent of diagnosed children have a family history of neuroblastoma. […] Although certain types of cancer have been linked to environmental factors, this is not true for neuroblastoma. Many research studies have been conducted to evaluate possible environmental causes, but no prenatal or environmental exposures have consistently or conclusively been associated with an increased risk of developing neuroblastoma. There is nothing parents could have done to prevent their child from developing this disease.

• #47

  https://link.springer.com/article/10.1023/A:1008998925889

  Objectives: We evaluated parental occupation and the risk of neuroblastoma using data from a large casecontrol study conducted by the Children’s Cancer Group and the Pediatric Oncology Group. […] Results: An increased risk of neuroblastoma was found for fathers employed as broadcast, telephone and dispatch operators (odds ratio [OR]=6.1; 95% confidence interval [CI]=0.750.9), electrical power installers and power plant operators (OR=2.7; CI=0.98.1), landscapers and groundskeepers (OR=2.3; CI=1.05.2), and painters (OR=2.1; CI=0.94.8). Elevated odds ratios were found for mothers employed as farmers and farm workers (OR=2.2; CI=0.68.8), florists and garden store workers (OR=2.4; CI=0.69.9), hairdressers and barbers (OR=2.8; CI=1.26.3), electric power installers and power plant operators, and sailors, fishers, and railroad workers.

• #48 Pediatric Neuroblastoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/988284-overview

  The cause of neuroblastoma is unknown, and no specific environmental exposure or risk factors have been identified. […] Because of young age of onset with this disease, investigators have focused on events before conception and during gestation. […] According to SEER data, factors investigated for which evidence is limited or inconsistent include medications, hormones, birth characteristics, congenital anomalies, previous spontaneous abortion or fetal death, alcohol or tobacco use, and paternal occupational exposures. […] The vast majority of neuroblastoma arises sporadically without family history of the disease. However, 1-2% of newly diagnosed cases do have a family history of neuroblastoma. Patients with familial neuroblastoma often present at earlier age or with several distinct primary tumors.

• #49 Causes of Neuroblastoma: New Warnings about Where You Live

  https://www.chem-tox.com/neuroblastoma/neuroblastoma.htm

  Neuroblastoma Links to Home Pesticides Agriculture by Richard Pressinger, M.Ed. Wayne Sinclair, M.D. Allergy, Asthma Immunology email: [email protected] […] The Chlordane Problem Evidence linking neuroblastoma with homes containing the pesticide chlordane […] Neuroblastoma Case Histories Doctors believe these child neuroblastoma cases resulted from chlordane exposure […] Home Pesticide Applications Linked to Neuroblastoma Using pesticides in and around homes has been found to increase the risk of developing neuroblastoma. This study is one of the largest and most thorough to date including efforts from over 7 Universities and research agencies. […] Because of the strong links of neuroblastoma and chlordane, it is very important that patients with neuroblastoma who are living in a home built before 1988 have their home tested for chlordane. […] Several major research studies are discussed below which have found immune system defects in children with neuroblastoma. The significance of this becomes apparent once it is understood that the immune system is responsible for removing cancer cells from the body. […] Unfortunately, many chemical compounds have been found to weaken immune system function – including pesticides used in agriculture and the pesticide chlordane, whose trace residues are still routinely found in indoor air in homes built prior to April, 1988. […] One of the largest studies to date has found that pesticide use around the home can more than double the chance of a child developing neuroblastoma. […] Results showed that using pesticides in and around the home resulted in a 60% increased likelihood of children developing the disease (Odds Ratio=1.6). […] It has been suggested that parental occupational exposures may increase the risk of neuroblastoma in offspring. Previous studies reported an association with paternal work in farming, and for mothers or fathers working as electricians or in electronics assembly and repair.

• #50 Pediatric Neuroblastoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/988284-overview

  The cause of neuroblastoma is unknown, and no specific environmental exposure or risk factors have been identified. […] Because of young age of onset with this disease, investigators have focused on events before conception and during gestation. […] According to SEER data, factors investigated for which evidence is limited or inconsistent include medications, hormones, birth characteristics, congenital anomalies, previous spontaneous abortion or fetal death, alcohol or tobacco use, and paternal occupational exposures. […] The vast majority of neuroblastoma arises sporadically without family history of the disease. However, 1-2% of newly diagnosed cases do have a family history of neuroblastoma. Patients with familial neuroblastoma often present at earlier age or with several distinct primary tumors.

• #51 Neuroblastoma: Practice Essentials, Background, Relevant Anatomy

  https://emedicine.medscape.com/article/439263-overview

  Increased risk of malignancies including neuroblastoma have been noted in children with various cancer predisposition syndromes, including Costello syndrome, Noonan syndrome, and neurofibromatosis type 1. […] Malignant transformation and maintenance of the dedifferentiated state of neural crest cells may result from failure of those cells to respond to normal signals that are responsible for normal morphologic differentiation. The factors involved in the cascade of events are poorly understood but most likely involve one or more ligand-receptor pathways. One of the most studied pathways is the nerve growth factor (NGF) and its receptor (NGFR). The dedifferentiated state of neuroblastoma leads to the variable presentations commonly observed in patients with neuroblastoma. […] Environmental and paternal exposures linked to neuroblastoma have not been identified.

• #52 Cell death-based treatment of neuroblastoma | Cell Death & Disease

  https://www.nature.com/articles/s41419-017-0060-1

  Neuroblastoma (NB) is the most common solid childhood tumor outside the brain and causes 15% of childhood cancer-related mortality. The main drivers of NB formation are neural crest cell-derived sympathoadrenal cells that undergo abnormal genetic arrangements. […] One of the major causes of sporadic NB is known to be MYCN amplification and mutations in ALK (anaplastic lymphoma kinase) are responsible for familial NB. […] Thus, MYCN amplification seems to be the major cause of sporadic NB and other mutations support tumor aggressiveness. […] The main drivers of NB formation are abnormalities in sympathoadrenal cells that derive from neural crest cells. […] Around 2% of NB cases appear to be hereditary, with ALK being the first gene identified to be responsible for familial NB. […] Furthermore, MYCN oncogene amplification is found in 20% of all NB cases, especially in patients who are resistant to therapy and have poor prognosis.

• #53 Neuroblastoma | Causes, Diagnosis & Treatment | Britannica

  https://www.britannica.com/science/neuroblastoma

  neuroblastoma, a tumour of the sympathetic nervous system (the branch of the autonomic nervous system that is best known for producing the fight-or-flight response) that affects young children. […] Much is known about the genetics and biology of neuroblastoma, and the development of therapies targeting the underlying biological mechanisms responsible for tumour growth is promising. […] Tumours associated with genetic abnormalities, such as amplification of an oncogene (a cancer-inducing gene) known as MYCN on chromosome 2 or loss of a part of chromosome 1 or 11, have been correlated with poor prognosis compared with tumours without such genetic changes. It is thought that such abnormalities are responsible, at least in part, for the development and progression of neuroblastoma.

• #54 Neuroblastoma: Practice Essentials, Background, Relevant Anatomy

  https://emedicine.medscape.com/article/439263-overview

  Increased risk of malignancies including neuroblastoma have been noted in children with various cancer predisposition syndromes, including Costello syndrome, Noonan syndrome, and neurofibromatosis type 1. […] Malignant transformation and maintenance of the dedifferentiated state of neural crest cells may result from failure of those cells to respond to normal signals that are responsible for normal morphologic differentiation. The factors involved in the cascade of events are poorly understood but most likely involve one or more ligand-receptor pathways. One of the most studied pathways is the nerve growth factor (NGF) and its receptor (NGFR). The dedifferentiated state of neuroblastoma leads to the variable presentations commonly observed in patients with neuroblastoma. […] Environmental and paternal exposures linked to neuroblastoma have not been identified.

• #55 Neuroblastoma: Practice Essentials, Background, Relevant Anatomy

  https://emedicine.medscape.com/article/439263-overview

  Increased risk of malignancies including neuroblastoma have been noted in children with various cancer predisposition syndromes, including Costello syndrome, Noonan syndrome, and neurofibromatosis type 1. […] Malignant transformation and maintenance of the dedifferentiated state of neural crest cells may result from failure of those cells to respond to normal signals that are responsible for normal morphologic differentiation. The factors involved in the cascade of events are poorly understood but most likely involve one or more ligand-receptor pathways. One of the most studied pathways is the nerve growth factor (NGF) and its receptor (NGFR). The dedifferentiated state of neuroblastoma leads to the variable presentations commonly observed in patients with neuroblastoma. […] Environmental and paternal exposures linked to neuroblastoma have not been identified.

• #56 Cell death-based treatment of neuroblastoma | Cell Death & Disease

  https://www.nature.com/articles/s41419-017-0060-1

  Neuroblastoma (NB) is the most common solid childhood tumor outside the brain and causes 15% of childhood cancer-related mortality. The main drivers of NB formation are neural crest cell-derived sympathoadrenal cells that undergo abnormal genetic arrangements. […] One of the major causes of sporadic NB is known to be MYCN amplification and mutations in ALK (anaplastic lymphoma kinase) are responsible for familial NB. […] Thus, MYCN amplification seems to be the major cause of sporadic NB and other mutations support tumor aggressiveness. […] The main drivers of NB formation are abnormalities in sympathoadrenal cells that derive from neural crest cells. […] Around 2% of NB cases appear to be hereditary, with ALK being the first gene identified to be responsible for familial NB. […] Furthermore, MYCN oncogene amplification is found in 20% of all NB cases, especially in patients who are resistant to therapy and have poor prognosis.

• #57 Cell death-based treatment of neuroblastoma | Cell Death & Disease

  https://www.nature.com/articles/s41419-017-0060-1

  Therefore, investigation of the MYCN gene amplification is considered to be a mandatory step for treatment specification. […] Changes in the ALK gene are identified as being responsible for ~50% of familial and ~1% of all NBs. […] The central role of the ALK in NB development makes it a possible target for NB treatment. […] Amplifications of the MYCN gene are known to be responsible for increased tumor growth, proliferation, and NB development. […] Therefore, downregulation of MYCN is one possible approach to induce apoptosis, decrease NB proliferation, and/or induce neuronal differentiation. […] Overexpression and amplifications of LIN28B are very common in NB cells and can in turn lead to high MYCN expression. […] Chromosomal copy number alterations are also represented in almost all NBs, for example, more than 50% have gain of 17q and 30% have loss of 1p36 and/or 11q.

• #58 Cell death-based treatment of neuroblastoma | Cell Death & Disease

  https://www.nature.com/articles/s41419-017-0060-1

  Therefore, investigation of the MYCN gene amplification is considered to be a mandatory step for treatment specification. […] Changes in the ALK gene are identified as being responsible for ~50% of familial and ~1% of all NBs. […] The central role of the ALK in NB development makes it a possible target for NB treatment. […] Amplifications of the MYCN gene are known to be responsible for increased tumor growth, proliferation, and NB development. […] Therefore, downregulation of MYCN is one possible approach to induce apoptosis, decrease NB proliferation, and/or induce neuronal differentiation. […] Overexpression and amplifications of LIN28B are very common in NB cells and can in turn lead to high MYCN expression. […] Chromosomal copy number alterations are also represented in almost all NBs, for example, more than 50% have gain of 17q and 30% have loss of 1p36 and/or 11q.

• #59 Pediatric Neuroblastoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/988284-overview

  Efforts are ongoing to investigate the incidence of ALK mutations across all subsets of neuroblastoma, but initial evidence indicates that somatic mutations of the ALK gene are also present in some cases of sporadic neuroblastoma. […] A 2014 study reported that deep-sequencing techniques can identify new ALK mutations at relapse of neuroblastoma, suggesting that patients would benefit from repeated tumor sampling. […] De Brouwer et al illustrate the occurrence of the ALK mutation specifically in neuroblastomas. […] Although they studied a small proportion of cases, mutations were found in similar frequencies in favorable and unfavorable outcome cases. […] The F1174L mutant was found more frequently in the poor outcome subgroup. […] This example illustrates the heterogeneity of cancer and the likely possibility that targeted therapies to the ALK gene may be of benefit in a subset of ALK cancers, which may possibly include a small subset of MYC-amplified neuroblastomas.

• #60 Cell death-based treatment of neuroblastoma | Cell Death & Disease

  https://www.nature.com/articles/s41419-017-0060-1

  Therefore, investigation of the MYCN gene amplification is considered to be a mandatory step for treatment specification. […] Changes in the ALK gene are identified as being responsible for ~50% of familial and ~1% of all NBs. […] The central role of the ALK in NB development makes it a possible target for NB treatment. […] Amplifications of the MYCN gene are known to be responsible for increased tumor growth, proliferation, and NB development. […] Therefore, downregulation of MYCN is one possible approach to induce apoptosis, decrease NB proliferation, and/or induce neuronal differentiation. […] Overexpression and amplifications of LIN28B are very common in NB cells and can in turn lead to high MYCN expression. […] Chromosomal copy number alterations are also represented in almost all NBs, for example, more than 50% have gain of 17q and 30% have loss of 1p36 and/or 11q.

• #61 Cell death-based treatment of neuroblastoma | Cell Death & Disease

  https://www.nature.com/articles/s41419-017-0060-1

  These arrangements have a strong correlation with MYCN amplification and poor prognosis. […] In many solid tumors, including NB, the outcome of the chemotherapeutic agents is also affected by the cellular stimulation/activation of autophagy, which can lead to unexpected consequences and autophagy-mediated cell survival or death. […] Therefore, inhibition of autophagy in combination with other apoptosis-inducing drugs is a potential strategy to induce apoptotic cell death of NB cells, especially in resistant tumors. […] Therefore, taking into account the importance of HIF-1 in NB tumor progression, the search for its inhibitors is a promising strategy.

• #62 Childhood Neuroblastoma | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/childhood-neuroblastoma

  Neuroblastoma likely develops from an early form of a nerve cell (called a neuroblast) found in the fetus. A genetic mutation inside the cell causes it to grow abnormally. Scientists continue to research the genetic abnormality to understand what causes the cancer. […] In rare cases, an inherited alteration in a specific gene causes neuroblastoma. The gene most commonly affected is the ALK gene, a protein-coding gene. Hereditary neuroblastoma accounts for 1 to 2 percent of cases. […] Our current research efforts focus on improving established neuroblastoma therapies, studying the disease’s genetic causes, and developing novel therapies. […] Our researchers have published some early work on the association between neuroblastoma and the ALK gene. Together with researchers at Children’s Hospital of Philadelphia, we are working on therapies that target this gene and improve neuroblastoma treatment.

• #63 Cell death-based treatment of neuroblastoma | Cell Death & Disease

  https://www.nature.com/articles/s41419-017-0060-1

  These arrangements have a strong correlation with MYCN amplification and poor prognosis. […] In many solid tumors, including NB, the outcome of the chemotherapeutic agents is also affected by the cellular stimulation/activation of autophagy, which can lead to unexpected consequences and autophagy-mediated cell survival or death. […] Therefore, inhibition of autophagy in combination with other apoptosis-inducing drugs is a potential strategy to induce apoptotic cell death of NB cells, especially in resistant tumors. […] Therefore, taking into account the importance of HIF-1 in NB tumor progression, the search for its inhibitors is a promising strategy.

• #64 Neuroblastoma: Symptoms & Causes | NewYork-Presbyterian

  https://www.nyp.org/pediatrics/cancer-care/neuroblastoma

  The cause of this cancer is unknown, and there are no known ways to prevent neuroblastoma. […] The exact cause of most neuroblastomas is not known. Most neuroblastomas are the result of changes in immature nerve cells called neuroblasts, which cause them to grow out of control. The causes of the change into cancer cells are currently unknown.

• #65 What is neuroblastoma? | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/childrens-cancer/neuroblastoma/about

  We dont know exactly what causes neuroblastoma. In some cases, there is a family history. But these cases are very rare. […] We dont know what causes, or how to prevent most childhood cancers. This includes neuroblastoma. No one should feel to blame.

• #66 Causes of Neuroblastoma | Genetics of Neuroblastoma | American Cancer Society

  https://www.cancer.org/cancer/types/neuroblastoma/causes-risks-prevention/what-causes.html

  In rare cases, neuroblastoma occurs as a result of gene changes inherited from a parent. […] It’s still not clear what causes many of the gene and chromosome changes that can lead to neuroblastoma. There are no known lifestyle-related or environmental causes of neuroblastomas, so it’s important to remember that there is nothing these children or their parents could have done to prevent these cancers.

• #67 Neuroblastoma in children – symptoms, treatments and causes | healthdirect

  https://www.healthdirect.gov.au/neuroblastoma-in-children

  Neuroblastoma is a cancer that affects young children. […] Researchers don’t completely understand what causes neuroblastoma. […] In rare cases, neuroblastoma can run in families and be associated with certain genetic conditions. […] We don’t completely understand what causes cancer in some children. However, if a child develops cancer, it’s not because of something they, or their parents did to cause it. No one is to blame if a child develops cancer.

• #68 Neuroblastoma: Genetic Risks Found

  https://www.icr.ac.uk/about-us/icr-news/detail/neuroblastoma-genetic-risks-found

  Scientists at The Institute of Cancer Research, led by Professor Nazneen Rahman, have been taking part in an international study into the causes of neuroblastoma, an aggressive childhood cancer. […] The researchers found that patients with the genetic alterations were more likely to develop aggressive neuroblastoma. […] Professor Rahman said: „This is an exciting development in our understanding of how neuroblastoma is caused. […] John M Maris, MD said: „Until now we have had very few clues as to what causes neuroblastoma. Our findings are very promising and lay the foundations for learning how genetic changes can lead to neuroblastoma.” […] The researchers will continue to collaborate in the future with the aim of better understanding the complex causes of neuroblastoma.

• #69 Childhood Neuroblastoma — Breast Cancer Hub

  https://www.breastcancerhub.org/cancer/childhood-neuroblastoma

  Even though there is a bit of research collected about this topic, more research and a better understanding of the genetic basis of the outcome disparities observed in children with neuroblastoma will further refine risk classification, and may also direct us to more effective, individualized treatment strategies.

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