Materiały źródłowe

• #1 Retinoblastoma – Wikipedia

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

  Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and 80% of retinoblastoma cases are first detected in those under 3 years old. […] Almost half of children with retinoblastoma have a hereditary genetic defect associated with it. In other cases, retinoblastoma is caused by a congenital mutation in the chromosome 13 gene 13q14 (retinoblastoma protein). […] Mutation of genes, found in chromosomes, can affect the way in which cells grow and develop within the body. Alterations in RB1 or MYCN can give rise to retinoblastoma. […] In children with the heritable genetic form of retinoblastoma, a mutation occurs in the RB1 gene on chromosome 13.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-Causes-Retinoblastoma.aspx

  Retinoblastomas are malignant tumors that occur mostly in children below 5 years of age. One of three tumors is bilateral. About 250-350 new cases are diagnosed each year in the US. Thus they make up about 4% of all tumors in childhood. […] Most of these tumors are caused by mutations in the RB1 gene, a tumor suppressor gene on chromosome 13. This gene is responsible for regulating the cell cycle so that cell proliferation proceeds in a planned and controlled fashion. […] RB1 mutations lead to the wild and erratic division of a single cell in the retina, which becomes a retinoblastoma. This may be influenced by other genetic changes which facilitate the persistence of this cancerous change. […] Retinoblastomas are due to either germinal (inheritable) or non-germinal (nonheritable) mutations in RB1. Germinal mutations are those which occur in every cell of the body, and are hereditary or transmissible.

• #3 Retinoblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545276/

  Retinoblastoma is primarily caused by mutations in the RB1 tumor suppressor gene located on chromosome 13q14. The RB1 gene encodes the retinoblastoma protein (pRB), a key regulator of the cell cycle. When both alleles of RB1 are mutated or inactivated, pRB loses its regulatory function, leading to unchecked retinal cell growth and tumor formation. […] In bilateral retinoblastoma, the mutation is germline in 98% of cases, although only 5% of cases have a family history. Approximately 95% of retinoblastoma cases occur sporadically, with 60% presenting as unilateral disease without an associated germline mutation. The remaining cases involve germline mutations, often resulting in multiple tumor development. […] The development of retinoblastoma follows Alfred Knudson’s 2-hit hypothesis. In hereditary cases, the 1st „hit” occurs when an individual inherits a defective RB1 allele as a germline mutation in all body cells. The 2nd „hit” is a somatic mutation that inactivates the remaining functional RB1 allele within retinal cells, triggering tumor formation. In nonhereditary cases, both mutations arise sporadically within retinal cells, leading to tumorigenesis.

• #4 Hereditary Retinoblastoma | St. Jude Care & Treatment

  https://www.stjude.org/care-treatment/treatment/genetic-syndromes/hereditary-retinoblastoma.html

  Retinoblastoma is caused by changes in a gene known as RB1. Genes carry important information that tells our bodys cells how to function. The RB1 gene controls how cells grow and divide. One of its main jobs is to prevent tumors from forming, particularly retinoblastoma. […] Cells from people with hereditary retinoblastoma carry 1 working copy of RB1 and 1 copy that is different. This difference (a mutation) causes the gene to not work right. When the remaining working copy of RB1 becomes damaged within a cell of the developing retina, it may lead to a retinoblastoma tumor. […] In about 10-20% of hereditary retinoblastoma cases, this mutation is passed down from a parent who also has hereditary retinoblastoma. In the other cases, the affected child has a new mutation that was not present in either parent. This child is the first in the family to have hereditary retinoblastoma. But they can now pass on the disease to 50% (1 in 2) of their future children.

• #5 Retinoblastoma | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/retinoblastoma?content_id=CON-20155330

  Retinoblastoma is caused by changes inside the cells in the eye. It’s not always clear what causes the changes that lead to this eye cancer. […] Retinoblastoma starts when cells in the eye get 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 also 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 make many more cells quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] For most instances of retinoblastoma, it’s not clear what causes the DNA changes that lead to cancer. However, it’s possible for children to inherit DNA changes from their parents. These changes can increase the risk of retinoblastoma.

• #6 Retinoblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545276/

  Retinoblastoma is primarily caused by mutations in the RB1 tumor suppressor gene located on chromosome 13q14. The RB1 gene encodes the retinoblastoma protein (pRB), a key regulator of the cell cycle. When both alleles of RB1 are mutated or inactivated, pRB loses its regulatory function, leading to unchecked retinal cell growth and tumor formation. […] In bilateral retinoblastoma, the mutation is germline in 98% of cases, although only 5% of cases have a family history. Approximately 95% of retinoblastoma cases occur sporadically, with 60% presenting as unilateral disease without an associated germline mutation. The remaining cases involve germline mutations, often resulting in multiple tumor development. […] The development of retinoblastoma follows Alfred Knudson’s 2-hit hypothesis. In hereditary cases, the 1st „hit” occurs when an individual inherits a defective RB1 allele as a germline mutation in all body cells. The 2nd „hit” is a somatic mutation that inactivates the remaining functional RB1 allele within retinal cells, triggering tumor formation. In nonhereditary cases, both mutations arise sporadically within retinal cells, leading to tumorigenesis.

• #7 Retinoblastoma – Causes, Symptoms, Diagnosis, Treatment & Prevention

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

  Retinoblastoma occurs in 2 forms a heritable and a non-heritable (sporadic) form. […] Heritable retinoblastoma indicates that the tendency to develop retinoblastoma is transmitted from parents to offspring, and accounts for 40% of the cases. […] The development of most cases of retinoblastoma may be explained by Knudsons two hit hypothesis. […] According to Knudsons two hit hypothesis, the DNA has to suffer two hits or two mutations for the cancer to occur. […] In the heritable type of retinoblastoma, one mutation is inherited from the parent, and so all the cells in the body have this mutation (germline mutation). The second mutation occurs later after fertilization in the retinal cells, resulting in retinoblastoma (somatic mutation). In the sporadic variety, both mutations occur within a single retinal cell after fertilisation of the egg (both are somatic mutations).

• #8 Retinoblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545276/

  Retinoblastoma is primarily caused by mutations in the RB1 tumor suppressor gene located on chromosome 13q14. The RB1 gene encodes the retinoblastoma protein (pRB), a key regulator of the cell cycle. When both alleles of RB1 are mutated or inactivated, pRB loses its regulatory function, leading to unchecked retinal cell growth and tumor formation. […] In bilateral retinoblastoma, the mutation is germline in 98% of cases, although only 5% of cases have a family history. Approximately 95% of retinoblastoma cases occur sporadically, with 60% presenting as unilateral disease without an associated germline mutation. The remaining cases involve germline mutations, often resulting in multiple tumor development. […] The development of retinoblastoma follows Alfred Knudson’s 2-hit hypothesis. In hereditary cases, the 1st „hit” occurs when an individual inherits a defective RB1 allele as a germline mutation in all body cells. The 2nd „hit” is a somatic mutation that inactivates the remaining functional RB1 allele within retinal cells, triggering tumor formation. In nonhereditary cases, both mutations arise sporadically within retinal cells, leading to tumorigenesis.

• #9 Retinoblastoma – Wikipedia

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

  The development of retinoblastoma can be explained by the two-hit model. According to the two-hit model, both alleles need to be affected, so two events are necessary for the retinal cell or cells to develop into tumors. […] Not all retinoblastoma cases are with RB1 inactivation. There are cases reported with only one RB1 mutation or even two functional RB1 alleles, which indicates other oncogenic lesions of retinoblastoma. Somatic amplification of the MYCN oncogene is responsible for some cases of nonhereditary, early-onset, aggressive, unilateral retinoblastoma.

• #10 Retinoblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545276/

  Hereditary cases account for approximately 45% of all retinoblastomas. These cases often present bilaterally or multifocally but within the same eye. Patients with a germline mutation in the RB1 gene face an increased risk of retinoblastoma and secondary malignancies, including osteosarcoma, soft tissue sarcomas, and melanoma. […] Sporadic cases account for approximately 55% of all retinoblastomas. These cases are typically unilateral and unifocal, meaning a single tumor develops in 1 eye. Unlike hereditary forms, both RB1 mutations occur sporadically within retinal cells without an underlying germline mutation. Since the mutation is not present in all body cells, patients are less likely to develop secondary malignancies. […] Retinoblastoma is a malignant tumor of the retina that primarily affects children younger than 5. The lesion’s development is strongly linked to genetic mutations that disrupt cellular growth and apoptosis regulation, leading to uncontrolled retinal cell proliferation. Understanding these genetic and molecular mechanisms provides critical insight into retinoblastoma pathogenesis and informs targeted approaches to diagnosis and treatment.

• #11 What is retinoblastoma? | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/retinoblastoma/what-is-retinoblastoma

  Retinoblastoma is caused by changes (mutations) in the retinoblastoma 1 (RB1) gene in the retinoblasts. Those mutations cause retinoblasts to grow out of control and form a tumour called retinoblastoma. […] There are 2 different types of retinoblastoma. The type depends on where and when the RB1 mutation occurs and whether the mutation is inherited. […] Non-hereditary retinoblastoma (also called sporadic retinoblastoma) happens by chance. About 60% of children with retinoblastoma have non-hereditary retinoblastoma. […] Hereditary retinoblastoma is passed on from a parent to a child. About 40% of children with retinoblastoma have hereditary retinoblastoma. […] In all cases of hereditary retinoblastoma, a child is born with one copy of the RB1 mutation in all cells of the body. A mutation of the second copy of the RB1 gene then occurs in retinoblast cells and causes retinoblastoma to form.

• #12 Retinoblastoma (Eye Cancer in Children) | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/retinoblastoma

  Retinoblastoma can occur in one of two forms: hereditary retinoblastoma and nonhereditary (sporadic) retinoblastoma. […] About 40 percent of retinoblastoma patients have the hereditary form of disease. Hereditary retinoblastoma is caused by alterations, also known as mutations, to specific areas within an individuals genetic information. […] In patients with hereditary retinoblastoma, the disorder develops as the result of alterations in a specific gene known as RB1, which is located on chromosome 13 at position q14.1-q14.2. […] The protein produced by the RB1 gene acts as a tumor suppressor, which means that it helps to keep cells from growing and dividing too quickly and it promotes cell death. […] Patients with hereditary retinoblastoma generally carry an alteration in one copy of the RB1 gene in all the cells of their body.

• #13 Retinoblastoma (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/retinoblastoma.html

  Retinoblastoma is a type of eye cancer that affects the retina, the inner layer of the eye. Nerve cells in the retina sense light and send images to the brain and allow us to see. […] Retinoblastoma causes tumors (clumps of cells) to grow in the retina. This happens when the nerve cells grow out of control. This means the eye can’t communicate with the brain as it should. […] Most cases of retinoblastoma are caused by a genetic mutation (a change in a gene). […] Heritable retinoblastoma can happen when: a child inherits a changed gene from a parent. Often, the baby will be born with retinoblastoma. […] a mutation happens spontaneously in a fetus during pregnancy. Most of these children will develop retinoblastoma before they are 1 year old. […] Heritable retinoblastoma usually affects both eyes and can cause more than one tumor in each eye. […] Sporadic retinoblastoma can happen because of a gene mutation in early childhood, usually after 1 year of age. Doctors don’t know what causes this change. Sporadic retinoblastoma usually affects just one eye.

• #14 Retinoblastoma (Eye Cancer in Children) | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/retinoblastoma

  Children with the hereditary form of retinoblastoma are also at a slightly increased risk to develop tumors in the pineal gland (a small gland located in the brain) and possibly another cancer, such as a bone or muscle cancer, later in life. […] Individuals with hereditary retinoblastoma who receive external beam radiation therapy have an increased risk (30-50 percent or higher) to develop second primary tumors, most commonly within the radiation field, over the course of their lives. […] About 60 percent of children with retinoblastoma have the non-hereditary form of the disease, which always manifests as a unilateral disease. […] It is believed that most children with non-hereditary disease develop a retinoblastoma tumor because both RB1 gene copies become damaged within a single developing retinal cell.

• #15 Retinoblastoma – EyeWiki

  https://eyewiki.org/Retinoblastoma

  Germline cases represent just over 1/3 of retinoblastoma cases. […] Patients with germline disease tend to have bilateral and multifocal tumors but may more rarely have unilateral disease. […] They also have a significantly increased risk for secondary tumors including primitive neuroendocrine tumors in the brain (so called “trilateral retinoblastoma” with pinealoblastoma). […] Finally, their offspring will have an increased risk of developing retinoblastoma, as this trait is transmitted in an „autosomal dominant” fashion with high penetrance (90%). […] Most unilateral tumors are sporadic and nonhereditary, but this is not always the case. About 15% of unilateral cases occur in individuals who have germline mutations. […] Genetic testing for RB1 mutations is recommended for all cases of retinoblastoma if possible. […] Patients with genetically detected RB1 mutations have greater risk of other malignancies later in life and require more vigilant screening for new retinoblastoma activity in both eyes as well as periodic MRI screening for primitive neuroendocrine tumor (PNET) activity.

• #16 Retinoblastoma | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/0315/p1039.html

  Retinoblastoma is a neuroblastic tumor that usually is detected in primary care. It is the most common primary intraocular malignancy of childhood, with an incidence of approximately one in 20,000, and affects males and females equally. The median age at diagnosis is 12 months in those with bilateral tumor and 24 months in those with unilateral disease. Onset after five years of age is rare, but retinoblastoma has been reported in adults. […] The retinoblastoma gene is a tumor suppressor gene, located on the long arm of chromosome 13 at region 14, that codes for the RB protein. Disease occurs from any mutation that inactivates both normal alleles. Approximately 60 percent of retinoblastoma occurrences are secondary to somatic, non-hereditary mutations. Such mutations result in predominantly unilateral, unifocal tumors. Approximately 40 percent of tumors result from germline mutations, either inheritance of a preexisting familial germline mutation (positive family history, 10 percent) or a new-onset germline mutation (negative family history, 30 percent). The typical inheritance pattern is of autosomal dominant type. […] Poor prognostic factors include a delay in tumor diagnosis, larger tumor, greater age, evidence of optic nerve involvement, and extraocular extension.

• #17 Retinoblastoma Risk Factors | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/pediatrics/cancer-care/types/retinoblastoma/risk-factors

  Ninety percent of all children who develop retinoblastoma are the first person in their family to have eye cancer. It is hard to explain why a child with no family history develops retinoblastoma. […] Retinoblastoma is caused by changes in a gene called RB1. […] About 40 percent of children with retinoblastoma have a hereditary form of the condition. Some children with hereditary retinoblastoma have inherited an RB1 mutation from a parent who had retinoblastoma as a child. […] The other 60 percent of children with retinoblastoma have a sporadic form of the condition, which cannot be passed to the next generation. […] Children with tumors in both eyes, known as bilateral tumors, are presumed to have hereditary retinoblastoma. This is due to a germline RB1 mutation that can be passed to the next generation.

• #18 What Causes Retinoblastoma? | Causes of Eye Cancer in Children | American Cancer Society

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

  There are very few known risk factors for retinoblastoma, but the main gene changes inside cells that can lead to retinoblastoma are now fairly well known. […] Certain changes in a persons DNA can cause cells of the retina to grow out of control. […] Cancers can be caused by DNA changes (mutations) that keep oncogenes turned on, or that turn off tumor suppressor genes. […] The most important gene in retinoblastoma is the RB1 tumor suppressor gene. […] About 1 in 3 children with retinoblastoma has a germline mutation in one RB1 gene; that is, the RB1 gene mutation is in all the cells in the body. […] About 9 of 10 children who are born with this RB1 germline mutation develop retinoblastoma. […] Most children with heritable retinoblastoma dont have an affected parent. […] Because children with this form of retinoblastoma have RB1 gene changes in all the cells in their body, they are also at higher risk for developing some other types of cancer.

• #19 Retinoblastoma | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-1-31

  Retinoblastoma is the first disease for which a genetic etiology of cancer has been described and the first tumor suppressor gene identified. […] Knudson in 1971 developed the hypothesis that retinoblastoma is a cancer caused by two mutational events. […] Loss or mutations of both alleles of the retinoblastoma gene RB1, localized to chromosome 13q1.4, are required to develop the disease. […] In hereditary cases (representing approximately 55% of the cases) patients carry a germline inactivated RB1 allele present in all cells in the body and somatic loss of the second allele in retinal cells. […] Germinal RB1 mutations with a high penetrance rate (90%) concern all patients with bilateral retinoblastoma as well as 15% of patients with the unilateral form. […] In non hereditary cases (45% of all patients) both RB1 alleles are inactivated somatically in a single developing retinal progenitor cell.

• #20 Retinoblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545276/

  Hereditary cases account for approximately 45% of all retinoblastomas. These cases often present bilaterally or multifocally but within the same eye. Patients with a germline mutation in the RB1 gene face an increased risk of retinoblastoma and secondary malignancies, including osteosarcoma, soft tissue sarcomas, and melanoma. […] Sporadic cases account for approximately 55% of all retinoblastomas. These cases are typically unilateral and unifocal, meaning a single tumor develops in 1 eye. Unlike hereditary forms, both RB1 mutations occur sporadically within retinal cells without an underlying germline mutation. Since the mutation is not present in all body cells, patients are less likely to develop secondary malignancies. […] Retinoblastoma is a malignant tumor of the retina that primarily affects children younger than 5. The lesion’s development is strongly linked to genetic mutations that disrupt cellular growth and apoptosis regulation, leading to uncontrolled retinal cell proliferation. Understanding these genetic and molecular mechanisms provides critical insight into retinoblastoma pathogenesis and informs targeted approaches to diagnosis and treatment.

• #21 What is retinoblastoma? | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/retinoblastoma/what-is-retinoblastoma

  Retinoblastoma is caused by changes (mutations) in the retinoblastoma 1 (RB1) gene in the retinoblasts. Those mutations cause retinoblasts to grow out of control and form a tumour called retinoblastoma. […] There are 2 different types of retinoblastoma. The type depends on where and when the RB1 mutation occurs and whether the mutation is inherited. […] Non-hereditary retinoblastoma (also called sporadic retinoblastoma) happens by chance. About 60% of children with retinoblastoma have non-hereditary retinoblastoma. […] Hereditary retinoblastoma is passed on from a parent to a child. About 40% of children with retinoblastoma have hereditary retinoblastoma. […] In all cases of hereditary retinoblastoma, a child is born with one copy of the RB1 mutation in all cells of the body. A mutation of the second copy of the RB1 gene then occurs in retinoblast cells and causes retinoblastoma to form.

• #22 Retinoblastoma: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1222849-overview

  When the initial mutation arises from a somatic cell (retinal), the patient has the nonhereditary type of retinoblastoma and the relatives have a low risk for the disease. […] When the initial mutation arises from the germline, the patient has the hereditary type of retinoblastoma and the relatives of the patient have a significant risk for retinoblastoma.

• #23 Retinoblastoma: Causes, Signs and Care | Banner Health

  https://www.bannerhealth.com/services/pediatrics/specialty-care/cancer/common-childhood-cancers/retinoblastoma

  Retinoblastoma is caused by a mutation in a gene called RB1. This happens mostly by chance (sporadic) but sometimes the changed gene is passed down (inherited) from a parent. […] Most cases of retinoblastoma happen randomly, meaning a child is not born with the gene change. Mutations in the RB1 gene are found only in the eye tumor cells, not every cell of the body. Sporadic retinoblastoma usually affects one eye. […] Genetic retinoblastoma occurs when a child is born with a mutation in the RB1 gene. The mutation affects all body cells, not just the eye. This type of retinoblastoma can affect one or both eyes. Children with this type have a higher risk of developing other cancers later in life.

• #24 Retinoblastoma Risk Factors | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/pediatrics/cancer-care/types/retinoblastoma/risk-factors

  Ninety percent of all children who develop retinoblastoma are the first person in their family to have eye cancer. It is hard to explain why a child with no family history develops retinoblastoma. […] Retinoblastoma is caused by changes in a gene called RB1. […] About 40 percent of children with retinoblastoma have a hereditary form of the condition. Some children with hereditary retinoblastoma have inherited an RB1 mutation from a parent who had retinoblastoma as a child. […] The other 60 percent of children with retinoblastoma have a sporadic form of the condition, which cannot be passed to the next generation. […] Children with tumors in both eyes, known as bilateral tumors, are presumed to have hereditary retinoblastoma. This is due to a germline RB1 mutation that can be passed to the next generation.

• #25 Retinoblastoma (Eye Cancer in Children) | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/retinoblastoma

  Children with the hereditary form of retinoblastoma are also at a slightly increased risk to develop tumors in the pineal gland (a small gland located in the brain) and possibly another cancer, such as a bone or muscle cancer, later in life. […] Individuals with hereditary retinoblastoma who receive external beam radiation therapy have an increased risk (30-50 percent or higher) to develop second primary tumors, most commonly within the radiation field, over the course of their lives. […] About 60 percent of children with retinoblastoma have the non-hereditary form of the disease, which always manifests as a unilateral disease. […] It is believed that most children with non-hereditary disease develop a retinoblastoma tumor because both RB1 gene copies become damaged within a single developing retinal cell.

• #26 What Causes Retinoblastoma? | Causes of Eye Cancer in Children | American Cancer Society

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

  Most of the remaining 2 out of 3 children with retinoblastoma do not have the RB1 gene mutation in all the cells of their body. […] Whether the changes in the RB1 gene are heritable or sporadic, its not clear what causes these changes. […] There are no known lifestyle-related or environmental causes of retinoblastoma, so its important to remember that there is nothing these children or their parents could have done to prevent these cancers.

• #27 Retinoblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545276/

  Although most retinoblastoma cases result from RB1 mutations, approximately 2% develop through RB1-independent mechanisms. Some nonhereditary cases involve amplification of the MYCN oncogene, which drives rapid cell proliferation and tumor growth. […] While genetic mutations primarily drive retinoblastoma development, certain nongenetic factors may influence disease risk. Advanced paternal age has been weakly associated with an increased likelihood of germline RB1 mutations, possibly due to accumulated DNA replication errors in sperm. Environmental mutagens, including radiation, chemical exposures, and other carcinogens encountered during pregnancy, have been suggested as potential contributors to sporadic mutations in fetal retinal cells. However, direct evidence linking these exposures to retinoblastoma remains limited.

• #28 Retinoblastoma Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq

  Retinoblastoma is a tumor that occurs in heritable (25%-30%) and nonheritable (70%-75%) forms. […] Heritable retinoblastoma is defined by the presence of a germline pathogenic variant of the RB1 gene. This germline pathogenic variant may have been inherited from an affected progenitor (25% of cases) or may have occurred in a germ cell before conception or in utero during early embryogenesis in patients with sporadic disease (75% of cases). The presence of positive family history or bilateral or multifocal disease is suggestive of heritable disease. […] The genomic landscape of retinoblastoma is driven by alterations in RB1 that lead to biallelic inactivation. A rare cause of RB1 inactivation is chromothripsis, which may be difficult to detect by conventional methods. […] The absence of detectable somatic RB1 variants in approximately 3% of unilateral, nonheritable retinoblastoma cases suggests that alternative genetic mechanisms may underlie the development of retinoblastoma.

• #29 Retinoblastoma: Etiology, Modeling, and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7465685/

  If cone cells are the cell-of-origin, why are these cells so susceptible to tumorigenic transformation? […] The intrinsic gene expression program of cone cells can be oncogenically activated in the absence of pRb. […] Cone-specific signal circuitry, including TR2, RXR, oncoprotein Mdm2 (MDM2), and N-myc proto-oncogene protein (MYCN), collaboratively supports the transition from premalignant to malignant lesions. […] A stable form of retinoma is uncommonly observed in clinics. […] Progressive genetic and epigenetic alterations superimposed on the cone circuitry may ultimately induce development of premalignant cells into highly proliferative retinoblastoma cells.

• #30 Second Gene Causes Retinoblastoma – DNA Science

  https://dnascience.plos.org/2013/03/21/second-gene-causes-retinoblastoma/

  In a list of famous genes, RB1 would probably be #1. Its the tumor suppressor gene whose loss of function is behind the childhood eye cancer retinoblastoma, and that Alfred Knudson investigated to deduce the 2-hit mechanism of cancer. […] A multinational team of researchers, led by Brenda Gallie of Impact Genetics and the Toronto Western Hospital Research Institute, discovered that in a very small proportion of children with retinoblastoma, an oncogene, MYCN, is the cause. […] About 1 in 20,000 infants has RB. In 40% of cases, both eyes develop tumors. This means that the child inherited a predisposition mutation in all cells, and the cancer develops when a second mutation hits a retinal cell. Of the 60% of cases where only one eye is affected, most (85%) result from 2 hits in the same retinal cell, without the inherited (aka germline or constitutional) mutation.

• #31 Retinoblastoma – Causes, Symptoms, Diagnosis, Treatment & Prevention

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

  Recently, another variety of retinoblastoma has been discovered, where the retinoblastoma gene was normal, but there was a high level of amplification of the MYCN gene only in the tumor cells. This does not result in heritable retinoblastoma, and these children do not have any of the characteristics of heritable retinoblastoma, including the risk of transmission to offspring.

• #32 Second Gene Causes Retinoblastoma – DNA Science

  https://dnascience.plos.org/2013/03/21/second-gene-causes-retinoblastoma/

  The road to finding the new gene began when the investigators in Toronto noticed that 7 children who had a tumor in just one eye didnt have the expected RB1 mutation. Instead, one of the genes that typically comes into play later in the disease is present in extra copies the oncogene MYCN. […] If an infant with a single tumor is diagnosed with MYCN RB, then its not heritable. These kids dont have the risk to pass it on to offspring, nor do they face a greater risk for subsequent cancers, Corson said. […] But in MYCN RB, since the disease is particularly aggressive, and the other eye will not become involved, surgical removal of the diseased eye is the correct therapeutic course, says Joan OBrien, MD, chair of ophthalmology at the University of Pennsylvania School of Medicine. […] Annotation of the human genome is revealing more instances of genetic heterogeneity, explaining people who have clear symptoms of a known genetic disease yet test negative like in retinoblastoma and osteogenesis imperfecta.

• #33 Risk factors for retinoblastoma | Canadian Cancer Society

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

  About 60% of retinoblastomas are non-hereditary. […] Hereditary retinoblastoma is passed on from a parent to a child. With hereditary retinoblastoma, a child is born with one copy of the RB1 mutation in all cells of the body. A mutation of the second copy of the RB1 gene occurs in retinoblasts causing retinoblastoma to form. […] About 40% of retinoblastomas are hereditary. […] A small number of children with retinoblastoma do not have an RB1 mutation. Instead, retinoblastoma is caused by an increased number of copies (called amplification) of the MYCN gene. Retinoblastoma related to MYCN causes large tumours in one eye and occurs in children younger than 6 months old.

• #34 Retinoblastoma: Etiology, Modeling, and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7465685/

  However, compared with other cancers including RB1-deficient malignancies, retinoblastoma exhibits minimal genomic instability because of unique cell type-specific circuitry. […] Genomic alterations in retinoblastoma are unique with common gains at 1q, 2p, and 6p and loss at 16q. […] Interestingly, the 1q gain and 16q loss in tumors are indicative of increased levels of genomic instability and associated with late diagnosis and non-hereditary retinoblastoma. […] Recurrent loss of 16q is believed to impair candidate suppressor genes and is implicated in advanced disease. […] Definitive determination of the cell-of-origin and understanding how tumor cells exploit the mechanisms of such susceptible cells for malignant transformation may facilitate development of treatments that specifically target tumor cells, while sparing normal retinal tissue.

• #35 Retinoblastoma: Etiology, Modeling, and Treatment

  https://www.mdpi.com/2072-6694/12/8/2304

  The cellular consequences of RB1 inactivation have been associated with multiple forms of genomic instability, which fuels tumorigenesis by eliminating safeguards that limit oncogenic transformation. […] Genomic alterations in retinoblastoma are unique with common gains at 1q, 2p, and 6p and loss at 16q. […] Interestingly, the 1q gain and 16q loss in tumors are indicative of increased levels of genomic instability and associated with late diagnosis and non-hereditary retinoblastoma. […] Recurrent loss of 16q is believed to impair candidate suppressor genes and is implicated in advanced disease. […] MYCN gain/amplification occurs in approximately 8% of retinoblastoma and is included in the most common focal genomic aberration. […] Studies have examined small genetic lesions by exon sequencing and revealed that mutations beyond RB1 are rare in retinoblastoma.

• #36 Retinoblastoma: Etiology, Modeling, and Treatment

  https://www.mdpi.com/2072-6694/12/8/2304

  The behavior of pRB-depleted cells in the normal retina together with histogenesis of retinoblastoma favors the concept of a cone cell-of-origin. […] If cone cells are the cell-of-origin, why are these cells so susceptible to tumorigenic transformation? […] The intrinsic gene expression program of cone cells can be oncogenically activated in the absence of pRb. […] Progressive genetic and epigenetic alterations superimposed on the cone circuitry may ultimately induce development of premalignant cells into highly proliferative retinoblastoma cells.

• #37 Retinoblastoma: Etiology, Modeling, and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7465685/

  If cone cells are the cell-of-origin, why are these cells so susceptible to tumorigenic transformation? […] The intrinsic gene expression program of cone cells can be oncogenically activated in the absence of pRb. […] Cone-specific signal circuitry, including TR2, RXR, oncoprotein Mdm2 (MDM2), and N-myc proto-oncogene protein (MYCN), collaboratively supports the transition from premalignant to malignant lesions. […] A stable form of retinoma is uncommonly observed in clinics. […] Progressive genetic and epigenetic alterations superimposed on the cone circuitry may ultimately induce development of premalignant cells into highly proliferative retinoblastoma cells.

• #38 Retinoblastoma: Etiology, Modeling, and Treatment

  https://www.mdpi.com/2072-6694/12/8/2304

  The behavior of pRB-depleted cells in the normal retina together with histogenesis of retinoblastoma favors the concept of a cone cell-of-origin. […] If cone cells are the cell-of-origin, why are these cells so susceptible to tumorigenic transformation? […] The intrinsic gene expression program of cone cells can be oncogenically activated in the absence of pRb. […] Progressive genetic and epigenetic alterations superimposed on the cone circuitry may ultimately induce development of premalignant cells into highly proliferative retinoblastoma cells.

• #39 Retinoblastoma: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1222849-overview

  Retinoblastoma is the most common primary ocular malignancy (eye cancer) of childhood. […] The most widely held concept of histogenesis of retinoblastoma holds that it generally arises from a multipotential precursor cell (mutation in the long arm of chromosome 13 band 13q14) that could develop into almost any type of inner or outer retinal cell. […] In 1970, Tso and colleagues established that the tumor arises from photoreceptor precursors. […] In October of 2007, a team of investigators at St. Jude Children’s Research Hospital (Memphis, Tenn) claimed to have identified the specific cell that gives rise to retinoblastoma. The major importance of this discovery is the idea that retinoblastoma can arise from fully matured nerves in the retina called horizontal interneurons, disproving the long-held scientific principle that fully formed, mature nerves cannot multiply like young immature cells.

• #40 Risk Factors for Retinoblastoma | American Cancer Society

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

  Most children diagnosed with retinoblastoma are younger than 3 years old. […] The risk of retinoblastoma is much higher in children with a parent who had the congenital (heritable) form of retinoblastoma. […] But for most children with retinoblastoma, there is no family history of the disease. […] On the other hand, children with the heritable form of retinoblastoma have a 1 in 2 chance of eventually passing on the RB1 gene change that causes the tumor to their children. […] Some studies have suggested some parental factors that might be linked to an increased risk of retinoblastoma, such as diets low in fruits and vegetables among mothers during pregnancy, exposure to chemicals in gasoline or diesel exhaust during pregnancy, exposure of fathers to radiation, and older age among fathers. […] The possible link between these factors and retinoblastoma is still being studied.

• #41 Who gets retinoblastoma? | Alex’s Lemonade Stand Foundation for Childhood Cancer

  https://www.alexslemonade.org/childhood-cancer/guides/childhood-cancer/chapter-5-retinoblastoma/who-gets-retinoblastoma

  The exact cause of retinoblastoma is unknown. However, much is known about the genetics and inheritance of this tumor. […] A change, called a mutation, in a gene called RB1 is involved in the development of retinoblastoma. […] The hereditary form of retinoblastoma occurs in around 40 percent of children with the disease. In these cases, the mutated RB1 gene is found in all the cells of the body. In 85 percent of children with the hereditary form of retinoblastoma, no one else in the family has retinoblastoma (called the non-familial or sporadic form). In these cases, a spontaneous mutation occurs in the copy of the RB1 gene when the child is conceived. The parents do not carry a mutation of the RB1 gene in every cell of their bodies. […] It is not known what causes the changes in the RB1 gene in either of these forms of retinoblastoma. It is known that there is nothing parents can do to prevent retinoblastoma. […] No environmental factors have been linked to increased risk of retinoblastoma.

• #42 Retinoblastoma: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/retinoblastoma

  There are two main ways that DNA errors that cause retinoblastoma can happen: Sporadic: This is when an error happens while your cells copy a parents DNA. […] Inherited: This is when one or both biological parents have DNA with the error. […] Inheriting a gene mutation also determines what form of retinoblastoma your child has. Inherited cases are usually bilateral and less often unilateral. […] A sibling of a child with retinoblastoma also has an increased chance of developing it. When both parents are unaffected by retinoblastoma, biological siblings of the affected child have a 4% to 7% risk of having retinoblastoma, too.

• #43

• #44 Risk Factors for Retinoblastoma | American Cancer Society

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

  Most children diagnosed with retinoblastoma are younger than 3 years old. […] The risk of retinoblastoma is much higher in children with a parent who had the congenital (heritable) form of retinoblastoma. […] But for most children with retinoblastoma, there is no family history of the disease. […] On the other hand, children with the heritable form of retinoblastoma have a 1 in 2 chance of eventually passing on the RB1 gene change that causes the tumor to their children. […] Some studies have suggested some parental factors that might be linked to an increased risk of retinoblastoma, such as diets low in fruits and vegetables among mothers during pregnancy, exposure to chemicals in gasoline or diesel exhaust during pregnancy, exposure of fathers to radiation, and older age among fathers. […] The possible link between these factors and retinoblastoma is still being studied.

• #45 Retinoblastoma | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-1-31

  A novel theory about the potential mechanism of retinoblastoma tumor development was proposed in response to the observation that spontaneous unilateral retinoblastoma may be more frequent in non industrialized countries. […] Environment (low folate intake during pregnancy) was also postulated to play a role in the risk of retinoblastoma occurrence because of the increased incidence of unilateral retinoblastoma in developing countries.

• #46 Retinoblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545276/

  Although most retinoblastoma cases result from RB1 mutations, approximately 2% develop through RB1-independent mechanisms. Some nonhereditary cases involve amplification of the MYCN oncogene, which drives rapid cell proliferation and tumor growth. […] While genetic mutations primarily drive retinoblastoma development, certain nongenetic factors may influence disease risk. Advanced paternal age has been weakly associated with an increased likelihood of germline RB1 mutations, possibly due to accumulated DNA replication errors in sperm. Environmental mutagens, including radiation, chemical exposures, and other carcinogens encountered during pregnancy, have been suggested as potential contributors to sporadic mutations in fetal retinal cells. However, direct evidence linking these exposures to retinoblastoma remains limited.

• #47 Retinoblastoma – Causes, Symptoms, Treatment, Diagnosis – MedBroadcast.com

  https://medbroadcast.com/condition/getcondition/retinoblastoma

  The main cause of retinoblastoma is through the sporadic form. About 90% of children with retinoblastoma have no previous family history of the disease. […] Retinoblastomas can be classified into 2 categories: one is caused by inheriting a defective gene (familial) and the other is caused by a random change in the RB gene during cell replication (sporadic). […] Family history is the main risk factor for retinoblastoma. Children who inherit the altered gene have a 90% risk of developing retinoblastoma. Smaller studies suggest that a parent infected with human papillomavirus (HPV) or a parent’s type of job or work exposure may increase the risk of their offspring developing retinoblastoma, but these two observations are controversial within the medical community.

• #48 Risk Factors for Retinoblastoma | American Cancer Society

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

  Most children diagnosed with retinoblastoma are younger than 3 years old. […] The risk of retinoblastoma is much higher in children with a parent who had the congenital (heritable) form of retinoblastoma. […] But for most children with retinoblastoma, there is no family history of the disease. […] On the other hand, children with the heritable form of retinoblastoma have a 1 in 2 chance of eventually passing on the RB1 gene change that causes the tumor to their children. […] Some studies have suggested some parental factors that might be linked to an increased risk of retinoblastoma, such as diets low in fruits and vegetables among mothers during pregnancy, exposure to chemicals in gasoline or diesel exhaust during pregnancy, exposure of fathers to radiation, and older age among fathers. […] The possible link between these factors and retinoblastoma is still being studied.

• #49 Retinoblastoma Types, Symptoms, Treatment, and Prognosis

  https://www.verywellhealth.com/retinoblastoma-5210489

  Retinoblastoma occurs when a tumor develops in some of the brains primitive nerve cells. Nearly 85% of unilateral (affecting one eye) retinoblastoma cases are referred to as sporadic, meaning that doctors do not know what caused them. In the other 15% of cases, the genetic predisposition has been inherited from one or both parents, even if they never had it themselves. […] Bilateral retinoblastoma (affecting both eyes) is usually hereditary. Trilateral retinoblastoma (affecting both eyes and pineal gland) is always hereditary. […] Whether mutations are inherited or sporadic, scientists do not know what causes them. Instead, they suspect random errors in gene transcription and have not identified any environmental or lifestyle causes. A 2023 study found about 5% of healthy people in families with a history of retinoblastoma carried the gene mutation but did not develop cancer.

• #50 Retinoblastoma – Diagnosis & Disease Information

  https://www.cancertherapyadvisor.com/ddi/retinoblastoma/

  Retinoblastoma accounts for approximately 3% of all childhood cancers. […] In more than 95% of cases, retinoblastoma is caused by a mutation in the RB1 gene, which is located on the 13q14 chromosome. […] There are 2 types of retinoblastoma: nonfamilial (sporadic) and familial (inherited). […] In 40% of cases, the disorder is hereditary and is autosomal dominant, meaning that a child would develop retinoblastoma if they receive the mutant gene from either parent. […] The other source of the disease is sporadic mutations with no family history; these tumors are usually unilateral. […] A hereditary mutation in the RB1 gene is the most important risk factor for developing retinoblastoma. […] Children with a family history of retinoblastoma have a greatly increased risk because if either parent has retinoblastoma, the defective gene will be passed on to their child. […] In addition, children who inherit the RB1 mutation are more likely to acquire other types of cancer later in life.

• #51 Retinoblastoma – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/retinoblastoma/diagnosis-treatment/drc-20351013

  Genetic testing for retinoblastoma looks for variations in a part of the DNA called the RB1 gene. […] Everyone with retinoblastoma has variations in the RB1 gene in their cancer cells. But some children with retinoblastoma have the RB1 gene variations in all of the cells in their bodies. This can happen if parents pass DNA variations to their child. The variations also can happen if something changes the RB1 gene as the child develops in the womb. […] If genetic testing shows your child has variations in the RB1 gene in all of the cells in the body, this helps the healthcare team plan your child’s treatment. Having variations in the RB1 gene in all of the cells also raises the risk of other kinds of cancer. Screening tests can help watch for those other kinds of cancer.

• #52 Retinoblastoma Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq

  Factors that influence the risk of subsequent neoplasms (SNs) include heritable retinoblastoma. Patients with heritable retinoblastoma have a markedly increased incidence of SNs, independent of treatment with radiation therapy. […] A possible association between the type of RB1 variant and incidence of SNs may exist, with complete loss of RB1 activity associated with a higher incidence of SNs.

• #53 Retinoblastoma | Ento Key

  https://entokey.com/retinoblastoma-11/

  Retinoblastoma is the result of a genetic mutation on chromosome 13. If the mutation is somatic, then the child can develop one tumor in one eye. If the mutation is in the germ line, the child is at risk for multifocal tumors in both eyes, with an average total of five retinoblastomas. There are no specific exposures that lead to this mutation, but research has identified advanced paternal age and possible paternal radiotherapy exposure as risks. […] The genetic mutation associated with retinoblastoma is found on chromosome 13 in the region 13q14. It is believed that this single locus exists for most forms of retinoblastoma. […] The most common second cancers associated with retinoblastoma include osteosarcoma (especially of the femur), cutaneous melanoma, and other sarcomas. Second cancers are believed to be related to germ-line mutation of chromosome 13. Second cancers present in 20% of germ-line mutation patients by 20 years and 50% by 50 years.

• #54 Diagnosing Retinoblastoma | NYU Langone Health

  https://nyulangone.org/conditions/retinoblastoma-in-children/diagnosis

  Retinoblastoma occurs when a gene mutationan alteration in a persons DNAcauses cells in the retina, called retinoblasts, to grow and multiply uncontrollably. The mutation occurs in a gene called RB1. […] Though retinoblastomas can be inherited, most are not. Children with a spontaneous, or nonhereditary, retinoblastoma typically develop a tumor in one eye. Children with the inherited type of retinoblastoma may have tumors in both eyes (bilateral tumors) and are at an increased risk for developing trilateral tumorsretinoblastoma in both eyes and also in the pineal gland of the brain. […] Children with bilateral or hereditary retinoblastoma are more likely to develop other types of cancer elsewhere in the body later in life. […] Doctors can use tumor samples collected during surgery or a blood test to look for mutations, or changes, in the gene RB1. This gene is the blueprint for a tumor suppressor protein present in cells in the eye and in tissues elsewhere in the body. Where on the gene this mutation occurs and whether its present at birth determine whether a child has the inherited form of retinoblastoma, which increases the risk of new tumors developing after treatment. […] The results of genetic testing not only affect the treatment for retinoblastoma but may also indicate the risk for this cancer in the childs family members.

• #55 Familial retinoblastoma due to intronic LINE-1 insertion causes aberrant and noncanonical mRNA splicing of the RB1 gene | Journal of Human Genetics

  https://www.nature.com/articles/jhg2015173

  The RB case reported here indicates that while standard mutational screening are effective to detect the majority of the mutations causing familial RB, ad hoc strategies should be achieved to resolve some cases. […] This study exemplified how an RNA-based mutation analysis in combination with massive parallel sequencing may be an effective method to identify retrotransposon insertions. […] We reported here the first case of familial RB caused by retrotransposition of a LINE-1 into RB1 gene and provided a comprehensive analysis of the effects caused by this LINE-1 insertion on RB1 mRNA splicing. […] We propose that in some cases a combination of RNA-based strategies and massive parallel sequencing can be useful to identify and characterize the causative mutation in hereditary diseases.

• #56 Retinoblastoma – EyeWiki

  https://eyewiki.org/Retinoblastoma

  Germline cases represent just over 1/3 of retinoblastoma cases. […] Patients with germline disease tend to have bilateral and multifocal tumors but may more rarely have unilateral disease. […] They also have a significantly increased risk for secondary tumors including primitive neuroendocrine tumors in the brain (so called “trilateral retinoblastoma” with pinealoblastoma). […] Finally, their offspring will have an increased risk of developing retinoblastoma, as this trait is transmitted in an „autosomal dominant” fashion with high penetrance (90%). […] Most unilateral tumors are sporadic and nonhereditary, but this is not always the case. About 15% of unilateral cases occur in individuals who have germline mutations. […] Genetic testing for RB1 mutations is recommended for all cases of retinoblastoma if possible. […] Patients with genetically detected RB1 mutations have greater risk of other malignancies later in life and require more vigilant screening for new retinoblastoma activity in both eyes as well as periodic MRI screening for primitive neuroendocrine tumor (PNET) activity.

• #57 Retinoblastoma Risk Factors | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/pediatrics/cancer-care/types/retinoblastoma/risk-factors

  Having hereditary retinoblastoma increases the risk of developing other cancers outside of the eye. These cancers include pinealoma (a tumor in the pineal gland in the brain), a type of bone cancer called osteosarcoma, cancers of soft tissues (such as muscle), and a form of skin cancer called melanoma. […] Genetic testing can help determine if your child has hereditary or sporadic retinoblastoma.

• #58 Familial retinoblastoma due to intronic LINE-1 insertion causes aberrant and noncanonical mRNA splicing of the RB1 gene | Journal of Human Genetics

  https://www.nature.com/articles/jhg2015173

  The RB case reported here indicates that while standard mutational screening are effective to detect the majority of the mutations causing familial RB, ad hoc strategies should be achieved to resolve some cases. […] This study exemplified how an RNA-based mutation analysis in combination with massive parallel sequencing may be an effective method to identify retrotransposon insertions. […] We reported here the first case of familial RB caused by retrotransposition of a LINE-1 into RB1 gene and provided a comprehensive analysis of the effects caused by this LINE-1 insertion on RB1 mRNA splicing. […] We propose that in some cases a combination of RNA-based strategies and massive parallel sequencing can be useful to identify and characterize the causative mutation in hereditary diseases.

• #59 Retinoblastoma: Etiology, Modeling, and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7465685/

  Retinoblastoma is a retinal cancer that is initiated in response to biallelic loss of RB1 in almost all cases, together with other genetic/epigenetic changes culminating in the development of cancer. […] The tumor is initiated through biallelic loss of tumor suppressor gene RB1 in more than 95% of cases, and develops after additional genetic/epigenetic changes. […] For this reason, cases of non-heritable retinoblastoma have unilateral tumors, unlike heritable retinoblastoma that often develops bilaterally and multifocally. […] Evidence suggests that retinoblastoma genesis is unique in humans. […] Thus, disease models should be appropriately used to study the disease and test therapies. […] The cellular consequences of RB1 inactivation have been associated with multiple forms of genomic instability, which fuels tumorigenesis by eliminating safeguards that limit oncogenic transformation.

• #60 Second Gene Causes Retinoblastoma – DNA Science

  https://dnascience.plos.org/2013/03/21/second-gene-causes-retinoblastoma/

  In a list of famous genes, RB1 would probably be #1. Its the tumor suppressor gene whose loss of function is behind the childhood eye cancer retinoblastoma, and that Alfred Knudson investigated to deduce the 2-hit mechanism of cancer. […] A multinational team of researchers, led by Brenda Gallie of Impact Genetics and the Toronto Western Hospital Research Institute, discovered that in a very small proportion of children with retinoblastoma, an oncogene, MYCN, is the cause. […] About 1 in 20,000 infants has RB. In 40% of cases, both eyes develop tumors. This means that the child inherited a predisposition mutation in all cells, and the cancer develops when a second mutation hits a retinal cell. Of the 60% of cases where only one eye is affected, most (85%) result from 2 hits in the same retinal cell, without the inherited (aka germline or constitutional) mutation.

• #61 Retinoblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545276/

  Hereditary cases account for approximately 45% of all retinoblastomas. These cases often present bilaterally or multifocally but within the same eye. Patients with a germline mutation in the RB1 gene face an increased risk of retinoblastoma and secondary malignancies, including osteosarcoma, soft tissue sarcomas, and melanoma. […] Sporadic cases account for approximately 55% of all retinoblastomas. These cases are typically unilateral and unifocal, meaning a single tumor develops in 1 eye. Unlike hereditary forms, both RB1 mutations occur sporadically within retinal cells without an underlying germline mutation. Since the mutation is not present in all body cells, patients are less likely to develop secondary malignancies. […] Retinoblastoma is a malignant tumor of the retina that primarily affects children younger than 5. The lesion’s development is strongly linked to genetic mutations that disrupt cellular growth and apoptosis regulation, leading to uncontrolled retinal cell proliferation. Understanding these genetic and molecular mechanisms provides critical insight into retinoblastoma pathogenesis and informs targeted approaches to diagnosis and treatment.

• #62 Retinoblastoma Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq

  Factors that influence the risk of subsequent neoplasms (SNs) include heritable retinoblastoma. Patients with heritable retinoblastoma have a markedly increased incidence of SNs, independent of treatment with radiation therapy. […] A possible association between the type of RB1 variant and incidence of SNs may exist, with complete loss of RB1 activity associated with a higher incidence of SNs.

• #63 What Causes Retinoblastoma? | Causes of Eye Cancer in Children | American Cancer Society

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

  Most of the remaining 2 out of 3 children with retinoblastoma do not have the RB1 gene mutation in all the cells of their body. […] Whether the changes in the RB1 gene are heritable or sporadic, its not clear what causes these changes. […] There are no known lifestyle-related or environmental causes of retinoblastoma, so its important to remember that there is nothing these children or their parents could have done to prevent these cancers.

• #64 All About Retinoblastoma | OncoLink

  https://www.oncolink.org/cancers/pediatric/information/retinoblastoma/all-about-retinoblastoma

  Retinoblastoma is rare childhood cancer, affecting about 300 children in the United States every year. […] Children who have a parent or sibling with this disease or children with a known mutation of chromosome 13q are at increased risk for developing retinoblastoma. […] Retinoblastoma occurs when there is a mutation to the retinoblastoma gene (RB or RB1). This is a tumor suppressor gene that acts as a brake on cell division. […] A child with congenital retinoblastoma has an abnormality in the RB1 gene. Congenital retinoblastoma happens in two ways. This mutation can be inherited from a parent, even if they never had retinoblastoma-they are a carrier of the mutated gene or there is a germline mutation of these genes during fetal development. […] Other than known genetic risk, there are no other known risk factors for retinoblastoma. There are no avoidable things you can do to prevent this cancer from happening.

Zobacz więcej