Materiały źródłowe

• #1 Ocular Melanoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK551647/

  Ocular melanoma, the second most prevalent form, manifests as a malignant growth of melanocytes in the eye’s uveal tract or conjunctiva. […] Although local treatments effectively prevent recurrence, nearly half of patients with uveal melanomas eventually experience metastatic disease. […] The emergence of targeted therapies presents a promising avenue for managing metastatic ocular melanoma, highlighting the dynamic aspects of its diagnosis and treatment. […] An increased risk of uveal melanoma is most significantly associated with ocular or oculodermal melanocytosis. […] Various genetic risk variants also exist. A recent discovery highlights a genetic correlation between uveal and cutaneous melanoma on chromosome 5p15.33. […] Present in 71% to 93% of patients affected by uveal melanoma, variations in the G-protein subunit alpha q (GNAQ) and G-protein subunit alpha 11 (GNA11) genes are the most common genetic variations.

• #2 Ocular Melanoma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26124

  An increased risk of uveal melanoma is most significantly associated with ocular or oculodermal melanocytosis. Individuals with light-colored eyes, fair skin, and skin that does not tan but burns easily are also at increased risk. The influence of ultraviolet (UV) light exposure remains unclear. If UV light exposure does cause an increased risk, the conferred risk is lower compared to its contribution to cutaneous melanoma. Additional risk factors include cutaneous nevi, cutaneous freckles, iris nevi, and arc welding. […] Various genetic risk variants also exist. A recent discovery highlights a genetic correlation between uveal and cutaneous melanoma on chromosome 5p15.33. Researchers believe that 2 potential genes in this area, telomerase reverse transcriptase (TERT) and CLPTM1 regulator of GABA type A receptor forward trafficking (CLPTM1L), may be responsible for conferring an increased risk of ocular melanoma. Recurrent mutations in the TERT promoter are associated with cutaneous melanoma. Other malignancies are associated with variants of CLPTM1L.

• #3 Ocular Melanoma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26124

  Present in 71% to 93% of patients affected by uveal melanoma, variations in the G-protein subunit alpha q (GNAQ) and G-protein subunit alpha 11 (GNA11) genes are the most common genetic variations. In addition, variations in BRCA1-associated protein 1 (BAP1), splicing factor 3b subunit 1 (SF3B1), and eukaryotic translation initiation factor 1A X-linked (EIF1AX) are also frequently encountered mutations. […] Genetic variations within BAP1, SF3B1, and EIF1AX affect prognosis. Patients with a BAP1 mutation or lacking BAP1 expression have a high risk of developing metastatic disease. An EIF1AX mutation is associated with a low risk of metastatic disease and a better prognosis. Additional indicators of poor prognosis include a gain of chromosome 8q and a loss of chromosome 3 or monosomy 3. […] Oxidative damage to pigmented tissues, controlled by the degree and type of iris pigmentation, is considered one of the primary mechanisms by which ocular melanoma develops. Primary ocular melanomas arise from melanocytes in the iris, choroid, ciliary body, and conjunctiva. Except for conjunctival melanoma, most evolve from preexisting nevi, but de novo growth is also possible.

• #4 Clinical Management of Uveal and Conjunctival Melanoma

  https://www.cancernetwork.com/view/clinical-management-uveal-and-conjunctival-melanoma

  Ocular melanoma is a rare but potentially devastating malignancy arising from the melanocytes of the uveal tract, conjunctiva, or orbit; it represents less than 5% of all melanoma cases in the United States. […] Uveal melanoma is characterized by activation of the mitogen-activated protein kinase (MAPK) pathway (among other signaling pathways) via mutations in GNAQ or GNA11. […] The molecular pathogenesis of uveal melanoma is distinct from that of cutaneous melanoma. […] Uveal melanoma is characterized by point mutations in the G protein -subunits GNAQ and GNA11. […] Mutations in GNAQ and GNA11 are found in about 80% of patients and are mutually exclusive. […] These G protein -subunits are normally inactivated by intrinsic GTPase activity; however, mutations in GNAQ and GNA11 disable their GTPase activity and result in constitutive activity, leading to activation of pathways that include the MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt pathways.

• #5

  https://link.springer.com/article/10.1007/s40487-018-0056-8

  In contrast to cutaneous melanomas, uveal melanoma lacks a mutation in the BRAF, NRAS, or KIT genes that influence MAPK signalling, suggesting that the two forms of melanoma occur via differing pathogenic pathways. […] Recent studies have demonstrated that mutations of the GNAQ, GNA11, PLCB4, and CYSLTR4 genes that encode members of the heterotrimeric G-protein alpha subunits may result in their constitutive G-protein activation and upregulation of the MAPK pathway in uveal melanoma. […] There is also evidence that the PI3K/AKT pathway, a commonly altered signalling pathway in human tumors, is also altered in uveal melanoma. […] The PI3K/AKT pathway is a cell survival mediator, and is negatively regulated by the tumor suppressor PTEN. […] PTEN is downregulated in uveal melanoma, promoting tumor cell survival.

• #6 Recent Advances in Molecular and Genetic Research on Uveal Melanoma

  https://www.mdpi.com/2073-4409/13/12/1023

  The primary driving forces in UM are early mutations in genes such as GNAQ/11, CYSLTR2 and PLCβ4 (so-called initiating mutations), followed by later mutations (so-called prognostic mutations, excluding MAPKAPK5) in genes such as SF3B1 (splicing factor 3B subunit 1), SRSF2 (serine- and arginine-rich splicing factor 2), MAPKAPK5 (MAPK activated protein kinase 5) and EIF1AX (eukaryotic translation initiation factor 1A X-linked), along with inactivating mutations in BAP1, a known tumor suppressor linked to a high risk of developing metastases when mutated. […] Activating mutations in GNAQ/11 genes are prevalent in approximately 85% of UM cases, leading to the activation of the MAPK pathway. This aberrant signaling drives UM progression and contributes to its malignancy. […] The JAK/STAT signaling pathway, a critical mediator in various cellular functions, has emerged as a significant player in the progression of cancer, including UM, where its aberrant activation has been linked to increased growth, survival, and malignancy of tumor cells.

• #7 Ocular Melanoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK551647/

  Genetic variations within BAP1, SF3B1, and EIF1AX affect prognosis. […] Patients with a BAP1 mutation or lacking BAP1 expression have a high risk of developing metastatic disease. […] An EIF1AX mutation is associated with a low risk of metastatic disease and a better prognosis. […] Oxidative damage to pigmented tissues, controlled by the degree and type of iris pigmentation, is considered one of the primary mechanisms by which ocular melanoma develops. […] Primary ocular melanomas arise from melanocytes in the iris, choroid, ciliary body, and conjunctiva. […] Choroidal melanomas typically manifest as dome-shaped tumors, resulting in multilayering of retinal pigment epithelial cells, accumulation of lipofuscin, drusen formation, and detachment of the retinal pigment epithelium. […] Choroidal melanomas tend to exert pressure on the lens, leading to astigmatism, cataracts, and subluxation.

• #8 Ocular Melanoma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26124

  Choroidal melanomas typically manifest as dome-shaped tumors, resulting in multilayering of retinal pigment epithelial cells, accumulation of lipofuscin, drusen formation, and detachment of the retinal pigment epithelium. In addition, phagocytic digestion of melanocyte debris induces patches of retinal pigment epithelium color change. These changes ultimately lead to choroidal neovascularization, subretinal exudation, hemorrhage, and fibrous plaque formation. […] Choroidal melanomas tend to exert pressure on the lens, leading to astigmatism, cataracts, and subluxation. In addition, sentinel vessels representing dilated episcleral vessels may be observed in some cases. […] Ocular melanoma exhibits 3 molecular forms: spindle, epithelioid, and mixed. Spindle cells are long and narrow and contain prominent nuclei and nucleoli. Epithelioid cells are larger, resembling epithelial cells, and contain eosinophilic cytoplasm. Occasionally, the tumor may be necrotic and unclassifiable. Spindle cell melanoma accounts for 9%, epithelioid for 5%, and mixed cell for 86%.

• #9 Molecular pathology of uveal melanoma | Eye

  https://www.nature.com/articles/eye2012255

  In most UM, the retinoblastoma (Rb) and p53 pathways are functionally inhibited, although actual mutations in the RB1 and TP53 genes are rare. […] The PI3K/AKT pathway is constitutively activated in most UM. […] The mitogen-activated protein kinase/extracellular signal-related kinase pathway (MAPK/ERK) pathway is essential for mediating cell-cycle progression, and in several types of cancer mutations in this pathway result in it being constitutively activated, producing inappropriate and autonomous proliferation of neoplastic cells. […] This puzzle concerning the MAPK pathway, and the mechanisms by which it was constitutively activated, persisted until the recent discovery of mutations in GNAQ in almost half of UM. […] GNAQ and GNA11 mutations are also found in uveal naevi and in most UM regardless of their tumour stage, chromosomal constellation or other outcome predictors.

• #9 Molecular pathology of uveal melanoma | Eye

  https://www.nature.com/articles/eye2012255

  Like other cancers, uveal melanomas (UM) are characterised by an uncontrolled, clonal, cellular proliferation, occurring as a result of numerous genetic, and epigenetic aberrations. […] Signalling pathways known to be disrupted in UM include: (1) the retinoblastoma pathway, probably as a result of cyclin D1 overexpression; p53 signalling, possibly as a consequence of MDM2 overexpression; and the P13K/AKT and mitogen-activated protein kinase/extracellular signal-related kinase pathway pathways that are disturbed as a result of PTEN and GNAQ/11 mutations, respectively. […] The identification of abnormal signalling pathways, genes and proteins in UM opens the way for target-based therapies, improving prospects for conserving vision and prolonging life. […] Intense efforts have been made in the last decades to understand the molecular genetics involved in the development and the progression of UM, to recognise those that are likely to metastasise, and to identify signalling pathways and possible druggable molecules in the neoplastic melanocytes, which can be targeted using systemic therapies.

• #10 Molecular characteristics of uveal melanoma and intraocular tumors (Review)

  https://www.spandidos-publications.com/10.3892/ol.2020.12270

  In UM, the MAPK signaling pathway is upregulated, which advocates for the presence of upstream mutations. […] Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) modulate regulation of cell proliferation, migration and survival. […] The most frequent mutations in GNAQ and GNA11 are considered to be the main driving events in UM.

• #10 Molecular characteristics of uveal melanoma and intraocular tumors (Review)

  https://www.spandidos-publications.com/10.3892/ol.2020.12270

  Despite the chromosome abnormalities, most UMs are considered to be caused by point mutations in G protein subunits, specifically in G protein subunit q (GNAQ) and G protein subunit 11 (GNA11), regardless of tumor stage or chromosomal constellation. […] It has been hypothesized that these mutations are early events in the pathogenesis of UM and are necessary for tumor malignancy. […] The PI3K/Akt/PTEN is one of the main molecular pathways involved in cell proliferation. It is mutated in multiple types of cancer and is constitutively activated in most UMs. […] Overall, these findings suggest that the PI3K/Akt/PTEN signaling pathway serves a vital role in UM progression; however, more research needs to be performed to fully understand its role. […] The MAPK/ERK pathway is crucial for mediating cell-cycle progression. In multiple cancer types, it is constitutively activated, resulting in proliferation of neoplastic cells.

• #11 Malignant Ocular Melanoma – BroadcastMed

  https://www.broadcastmed.com/4561/videos/malignant-ocular-melanoma

  I’m going to speak now about malignant melanoma of the eye. What is ocular melanoma? It’s the most common form of primary adult eye cancer. It involves the pigmented portions of the eye, the iris, the choroid, and the ciliary body. It’s also known as uveal melanoma, as these pigmented portions of the eye are called the uveal tract. […] Distinct genetic alterations exist in uveal melanoma, compared to cutaneous melanoma. BRAF mutations are more common in cutaneous melanoma. Recently, we’ve identified mutations in signaling proteins, GNAQ and GNA11 as early or initiating events in ocular melanoma. […] GNAQ mutations cause a change in guanine nucleotide-binding protein alpha-q. This signaling protein activates the MAP kinase pathway, which is the same pathway which is activated through a different mechanism in cutaneous melanoma.

• #12

  https://link.springer.com/article/10.1007/s40487-018-0056-8

  The RAF/ERK/MEK and PI3K/AKT pathways are also activated by the insulin-like growth factors (IGFs) through their interaction with the insulin-like growth factor-1 receptors (IGFR1). […] An inactivating somatic mutation of the BRCA-1 associated protein (BAP1) has been implicated in the progression of uveal melanoma, as the mutation is present in 84% of metastasizing tumors. […] Germline mutations in BAP1 have been observed in 5% of uveal melanomas and have been associated with larger tumor size and ciliary body involvement. […] Two recurrent mutations that are associated with a positive prognosis have been identified in patients with primary uveal melanoma. […] The first is a recurring mutation occurring at codon 625 of the SF3B1 gene, which encodes the splicing factor 3B subunit 1.

• #13 Clinical Management of Uveal and Conjunctival Melanoma

  https://www.cancernetwork.com/view/clinical-management-uveal-and-conjunctival-melanoma

  GNAQ was recently shown to stimulate the transcriptional coactivator Yes-associated protein (YAP) through the TrioRho/Rac signaling circuit, which promotes the polymerization of globular actin to filamentous actin, independent of the canonical Hippo pathway. […] Significant effort has been made to better elucidate the biological mechanisms driving distant spread and growth. […] A number of growth factor receptors, such as c-Met, c-Kit, and insulin growth factor receptor 1, have been implicated in the metastatic progression of uveal melanoma. […] The protein MDA-9/syntenin-1 (melanoma differentiation associated gene 9/syndecan-binding protein 1), encoded by the SDCBP gene, may also be involved in metastatic dissemination via increased hepatocellular growth factor-mediated invasion (activation of focal adhesion kinase [FAK], Akt, Src).

• #14 Uveal Melanoma: Comprehensive Review of Its Pathophysiology, Diagnosis, Treatment, and Future Perspectives

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11352094/

  Furthermore, recent studies have underscored the importance of circulating neoplastic-immune hybrid cells (CHCs) in the blood corresponding to dual nature hybrid cells (DNCs) in the primary tumor and tumor-derived extracellular vesicles (TEVs) in the pathogenesis of metastatic UM. […] The emergence of novel diagnostic modalities, such as liquid biopsies, which consist of obtaining from the peripheral blood circulating tumor cells and other derived molecules, has opened doors to better patient care and disease outcome. […] The genomic instability ensuing this phenomenon promotes tumor growth and proliferation and subsequent hematogenous spread. […] The inflammatory phenotype of UM, which is defined as a lymphocytic inflammatory process, is known to be associated with a poor prognosis.

• #14 Uveal Melanoma: Comprehensive Review of Its Pathophysiology, Diagnosis, Treatment, and Future Perspectives

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11352094/

  Activation of the NFB pathway was found to occur in primary and metastatic UM, subsequently upregulating UM cell proliferation and inhibiting apoptosis. […] TEVs favor tumorigenesis through the transfer of their material to neighboring cells. […] The oncogenic potential of TEVs in metastatic disease has been proposed as a mechanism for UM dissemination. […] CHCs are a novel tumor cell population found within the TME recently identified in the blood of patients with UM. […] They result from the fusion of tumor cells with leucocytes and form the backbone of tumor heterogeneity.

• #15 Uveal Melanoma: Comprehensive Review of Its Pathophysiology, Diagnosis, Treatment, and Future Perspectives

  https://www.mdpi.com/2227-9059/12/8/1758

  The inflammatory phenotype of UM, which is defined as a lymphocytic inflammatory process, is known to be associated with a poor prognosis. Lymphocytic infiltration is marked by an increase in lymphocytes, macrophages, and HLA class I and II expression. The nuclear factor-κB (NFκB) is a known regulator of the innate and adaptative immune system, with a significant role in inflammation homeostasis. Activation of the NFκB pathway was found to occur in primary and metastatic UM, subsequently upregulating UM cell proliferation and inhibiting apoptosis. […] A major constituent of the TME are TEVs, which are known to bridge the communication between tumor cells and their microenvironment. TEVs favor tumorigenesis through the transfer of their material to neighboring cells. They are cell-secreted vesicles that encompass various bioactive substances, such as nucleic acids (e.g., DNA and RNA), lipids, proteins, and metabolites.

• #16 Uveal Melanoma: Comprehensive Review of Its Pathophysiology, Diagnosis, Treatment, and Future Perspectives

  https://www.mdpi.com/2227-9059/12/8/1758

  Studies have shown that the concentration of UM-derived EVs in the blood is comparable to that found in the aqueous humor and vitreous humor. Therefore, given their abundance in peripheral blood and subsequent ease in obtaining samples for testing, they have thus become an exciting avenue as a diagnostic tool. The oncogenic potential of TEVs in metastatic disease has been proposed as a mechanism for UM dissemination. […] CHCs are a novel tumor cell population found within the TME recently identified in the blood of patients with UM. They highly express the markers gp100 (a melanocytic marker), HTR2b (a cell surface serotonin receptor), and CD45 (a leukocyte common antigen). They result from the fusion of tumor cells with leucocytes and form the backbone of tumor heterogeneity. It was shown in other cancers that the fusion of tumor cells with macrophages induces a hybrid that exhibits a mixed phenotype and differential response to the TME.

• #17 Uveal Melanoma: Comprehensive Review of Its Pathophysiology, Diagnosis, Treatment, and Future Perspectives

  https://www.mdpi.com/2227-9059/12/8/1758

  Uveal melanoma (UM) is the most common intraocular malignancy in adults. Recent advances highlight the role of tumor-derived extracellular vesicles (TEV) and circulating hybrid cells (CHC) in UM tumorigenesis. […] Frequent mutations in the BAP1 (i.e., BRCA-1 associated protein 1), EIF1AX (i.e., eukaryotic translation initiation factor 1A X-linked), GNA11 (i.e., guanosine nucleotide-binding protein alpha-11), GNAQ (i.e., guanosine nucleotide-binding protein Q), and SF3B1 (i.e., splicing factor 3b subunit 1) genes were shown to occur in the majority of UM cases, as well as contribute on different levels to the metastatic risk. Mutations in the GNAQ and GNA11 signaling pathways are known to drive neoplastic growth and proliferation through RAS and PI3K molecular signaling networks. […] Furthermore, recent studies have underscored the importance of circulating neoplastic-immune hybrid cells (CHCs) in the blood—corresponding to dual nature hybrid cells (DNCs) in the primary tumor—and tumor-derived extracellular vesicles (TEVs) in the pathogenesis of metastatic UM. CHCs, generated by cell fusion, are neoplastic cells that express combined neoplastic and immune cell features, which makes their identification possible through co-expression of tumor and leukocyte cell-surface markers. Their presence in the bloodstream of affected patients can be used to assess metastatic UM risk.

• #18 Ocular Melanoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK551647/

  Ocular melanoma exhibits 3 molecular forms: spindle, epithelioid, and mixed. […] Staining for S-100, a multigenic family of small acidic EF-hand calcium-binding proteins, is highly sensitive for identifying melanoma. […] Local treatment prevents local recurrence in 95% of patients. However, due to micrometastasis, 50% of patients with uveal tumors develop metastatic disease. […] Chromosomal analysis identifying monosomy 3 and 8q gain can help determine prognosis to some extent, but gene expression profiling proves to have better prognostic abilities. […] The overall mortality for choroidal melanoma and ciliary body melanoma is 30% to 50% within 10 years, primarily due to metastatic disease.

• #19 Choroidal Melanoma: Practice Essentials, Overview, Pathophysiology

  https://emedicine.medscape.com/article/1190564-overview

  The tumors disruption of choroidal circulation and consequent ischemia typically cause degeneration of retinal photoreceptors and other retinal neurons. […] Choroidal melanoma ultimately causes death, practically always secondary to distant metastases rather than local spread. Its metastatic potential depends on the histopathologic aggressiveness of the tumor cells. […] If the melanoma does not show extraocular extension, it can only spread hematogenously, because there are no lymphatic vessels in the eye. It most often metastasizes to the liver; other organs of dissemination include the lung, bone, skin, and central nervous system (CNS). […] Less frequently, choroidal melanoma can grow transsclerally, through emissary channels, and metastasize locally into the orbit or rarely the conjunctiva.

• #20 Metastatic disease from uveal melanoma: treatment options and future prospects | British Journal of Ophthalmology

  https://bjo.bmj.com/content/101/1/38

  Inactivating BAP1 mutations increase the prometastatic behaviour of uveal melanoma cells, although the mechanism by which this occurs remains unknown. […] Survival prognostication takes into account clinical predictors, pathological predictors and genetic predictors. […] Despite the development of effective local therapies, 5-year survival rates have not changed in the past three decades and up to 50% of patients develop metastases. […] The risk of developing metastatic disease is determined by multiple factors, including tumour size, location and genetic profile. […] For those patients who do develop metastatic disease, there is as yet no proven standard of care. […] Given the molecular profile of uveal melanoma, there is a rationale for treatments that target downstream components of the molecular pathways driving tumour growth, including MEK and protein kinase C (PKC). […] Activating somatic mutations in GNAQ led to the constitutive activation of the downstream PKC pathway PLC/PKC/ERK1/2. […] The combination of binimetinib and AEB071 is being investigated in a phase Ib/II trial in patients with metastatic uveal melanoma.

• #21 Uveal Melanoma—Molecular Basis and Potential Treatment Targets | touchOPHTHALMOLOGY

  https://touchophthalmology.com/ocular-oncology/journal-articles/uveal-melanoma-molecular-basis-and-potential-treatment-targets/

  These differences present an opportunity and challenge for the future development of therapeutic interventions. […] These data convincingly demonstrate that GNAQ and GNA11 are oncogenes in uveal melanoma, and targeting these genes (or protein products) or downstream signaling mediators may be a viable treatment strategy. […] The identification of gene aberrations that result in loss of BAP1, a previously described tumor suppressor located on chromosome 3p21.1, in a large number of primary uveal melanoma tumors with monosomy 3 provided strong evidence that BAP1 loss may be a very important mediator of metastatic disease. […] Given the propensity of uveal melanoma to metastasize to the liver, many investigators have hypothesized that the liver microenvironment may contain factors that are hospitable to uveal melanoma growth.

• #22 Eye melanoma – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/eye-melanoma/symptoms-causes/syc-20372371

  Eye melanoma happens when cells in the eye develop changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA tells the cells to grow and multiply at a set rate. The DNA also tells 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 tissue. In time, cancer cells can break away and spread to other parts of the body. When cancer spreads, it’s called metastatic cancer.

• #23 Uveal melanoma: epidemiology, etiology, and treatment of primary disea | OPTH

  https://www.dovepress.com/uveal-melanoma-epidemiology-etiology-and-treatment-of-primary-disease-peer-reviewed-fulltext-article-OPTH

  The Hippo pathway acts through the proteins YAP and TAZ to activate the transcription factors TEAD and SMAD. […] These multiple pathways provide an array of targets that are being studied for therapeutic intervention. The various parallel pathways suggest a role for combination therapy, with clinical studies under way for metastatic disease. […] In addition to the genetic alterations described above, epigenetic factors, including DNA methylation, histone modification, and alterations in noncoding RNA, are increasingly felt to play a role in the development of UM. […] Tumor suppressors, such as RASSF1A, and other molecules, such as the adhesion protein E-cadherin, are hypermethylated in 50%70% of UM, correlate with metastatic disease, and may provide potential novel therapeutic strategies.

• #24 Uveal melanoma: epidemiology, etiology, and treatment of primary disea | OPTH

  https://www.dovepress.com/uveal-melanoma-epidemiology-etiology-and-treatment-of-primary-disease-peer-reviewed-fulltext-article-OPTH

  MicroRNAs (miRNAs) inhibit translation of complementary coding RNA and may act intracellularly, or when packaged in exosomes are capable of traveling in blood and modifying activity of distant cells. […] miR-124, miR-137, and miR-34b/c act as tumor suppressors by inhibiting oncogenes and are downregulated in UM, whereas many miRNAs, like miR-20a, -25b, -146a, and 199a, are overexpressed and may promote metastatic progression, in these examples likely through immunosuppression.

• #25 Update on uveal melanoma: Translational research from biology to clinical practice (Review)

  https://www.spandidos-publications.com/10.3892/ijo.2020.5140

  Hypoxia is an essential mechanism for a number of carcinogenic processes and is an important factor to consider when designing more effective therapies for various tumours. […] In uveal melanoma, hypoxia has been associated with numerous alterations. […] Collectively, these data identify hypoxia as an important factor to consider in the treatment of uveal melanoma, warranting further investigation. […] Oxidative stress is a cell condition that arises from an imbalance of oxidizing molecules produced mainly via mitochondrial respiration, and of reducing molecules, also known as antioxidants. […] The role of oxidative stress in the development of cancer is, however, still a somewhat controversial issue. […] In uveal melanoma, the overexpression of transcription factors, such as HES1 has been directly involved in the metastatic capacity of uveal melanoma, suggesting the methylation of the promotor region of histone H3K4 is an inducer of this over-expression. […] The search for novel and more reliable blood or tissue biomarkers could be expedited by developments in techniques of proteomics and metabolomics, that will allow for the analysis of larger and more representative samples from patients with uveal melanoma.

• #26 Update on uveal melanoma: Translational research from biology to clinical practice (Review)

  https://www.spandidos-publications.com/10.3892/ijo.2020.5140

  Uveal melanoma is the most common type of intraocular cancer with a low mean annual incidence of 510 cases per million. […] As in cutaneous melanoma, tumours arise in melanocytes; however, the characteristics of uveal melanoma differ, accounting for 35% of melanocytic cancers. […] The anatomopathological study of uveal melanoma has recently benefited from developments in molecular biology. […] In effect, disease classification or staging according to molecular profile is proving useful for the assessment of this type of tumour. […] Further, the improved knowledge of tumour biology is giving rise to a more targeted approach to diagnosis, prognosis and treatment development; for example, epigenetics driven by microRNAs as a target for disease control. […] Uveal melanoma has a large number of associated risk factors such as age, sex, genetic or phenotypic predisposition, the work environment and dermatological conditions.

• #27 Novel Risk Factors Identified for Uveal Melanoma

  https://www.reviewofoptometry.com/news/article/novel-risk-factors-identified-for-uveal-melanoma

  The authors discuss in their writing that many known risk factors like white race, light skin and eye color suggest an important role of UV light exposure in UM pathogenesis. […] The authors further discuss some risks in their writing. Of interest was the novel finding of eye trauma. They note that there was no clinical difference seen in surveillance pattern for patients with prior eye trauma before diagnosis of UM. […] Because of the germline mutations seen in certain genes, which are often associated with hereditary malignancies, the authors also recommend thorough characterization of the family cancer tree and genetic testing may be warranted in adolescents and young adults with newly diagnosed UMs to inform the necessity of screening for other malignancies.

• #28 Ocular Melanoma Risk Factors – AIM at Melanoma Foundation

  https://www.aimatmelanoma.org/melanoma-101/types-of-melanoma/ocular-melanoma-riskfactors/

  Ocular melanoma is rare, accounting for only about 3 to 4% of all melanomas. […] The cause of ocular melanoma is not known, but several risk factors have been identified. […] Risk increases with age. It is slightly more common in men than in women. […] Ocular melanoma is more common in people with fair skin, frequent sunburns, and/or light-colored eyes. […] Although the risk factors for uveal melanoma are generally similar to the known risk factors for skin melanoma, uveal melanoma is not thought to be caused by the sun. […] Certain inherited medical conditions are linked to having a higher risk of ocular melanoma. […] Exposure to UV rays from the sun is a well-known risk factor for skin melanoma. […] There is some evidence linking UV exposure to some of the subtypes ocular melanoma (possibly uveal melanoma of the iris and conjunctival melanoma), but the majority of ocular melanomas are not linked to UV exposure.

• #29 New Aspects on the Pathogenesis of Conjunctival Melanoma | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-540-33681-5_11

  Conjunctival melanoma shares many clinical, epidemiological and molecular features with cutaneous but not uveal melanoma. […] There is substantial evidence implicating ultraviolet radiation (UVR) as inducing conjunctival melanoma, probably through the mitogen-activated protein kinase pathway. […] Because conjunctival melanoma occasionally arises in parts of the conjunctiva protected from UVR exposure, alternative pathways may exist.

• #30 Distribution of GNAQ and GNA11 Mutation Signatures in Uveal Melanoma Points to a Light Dependent Mutation Mechanism | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138002

  Uveal melanomas (UM) originate from melanocytes in the interior wall of the eye, namely from the iris, ciliary body and the choroid with marked differences in light exposure (from dark anterior to illuminated posterior). […] In this report choroidal, ciliochoroidal and iridociliary melanomas were analyzed for GNAQ and GNA11 mutations which were subsequently correlated to the location of tumor origin. […] Combined these data suggest a light and a pigment dependent etiology in UM development. […] The mechanisms that generate the mutations in CM and UM are largely unknown. […] We report that the GNAQ Q209P mutation is almost exclusively detected in choroidal melanoma that originate from the posterior region. This is the region in the eye that is most exposed to focused light and we therefore hypothesize that damaging visible light is involved in choroidal melanoma development.

• #31 Distribution of GNAQ and GNA11 Mutation Signatures in Uveal Melanoma Points to a Light Dependent Mutation Mechanism | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138002

  A2E induced 8-oxo-deoxyguanosine that is incorporated in DNA replication, may lead to the GNAQ Q209P (AC) mutation in a successive round of replication. […] Combined, GNAQ and GNA11 mutation distribution analysis suggests both location-specific and generic mutation mechanisms in UM. We propose that light-induced damage may underlie the almost exclusive presence of the GNAQ Q209P mutation in choroidal melanoma.

Zobacz więcej