Uveal melanoma pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.,Simrat Sarai, M.D. [2]
Overview
Genes involved in the pathogenesis of uveal melanoma include GNAQ, GNA11, and BAP1.
Pathophysiology
Pathogenesis
- It is understood that uveal melanoma is the result of genetic mutations.
- Uveal melanoma arises from melanocytes, which are normally involved in melanin production.
Genetics
Genes involved in the pathogenesis of uveal melanoma include:
- Activating mutations in GNAQ or GNA11, genes encoding for G protein alpha subunits. [1][2][3]
- These mutations lead to activation of downstream signaling pathways including the MAPK pathway in uveal melanoma.
- Inactivating somatic mutations are present in the gene encoding BRCA1-associated protein 1 (BAP1) on chromosome 3p21.1.
- The mutations in the gene BAP1 are strongly linked to metastatic spread and patient survival.[4]
- In approximately five percent of patients with uveal melanomas germline mutations have been identified in BAP1, and these have been associated with involvement of the ciliary body and larger tumors.[5]
- In approximately 18.6 percent of primary uveal melanomas recurring mutations occurring exclusively at codon 625 of the SF3B1 gene, encoding splicing factor 3B subunit 1 were identified.[6]
Associated Conditions
Conditions associated with uveal melanoma include:[7]
- Ocular nevi
- Impaired immune system
- Pregnancy
- Trauma
Gross Pathology
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
On microscopic histopathological analysis, we have 5 subtypes according to cell type into: Spindle A, spindle B, epitheliolid, mixed, and necrotic.
| Cell type | Explanation |
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| Spindle A |
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| Spindle B |
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| Epithelioid |
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| Mixed |
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| Necrotic |
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References
- ↑ 1.0 1.1 Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T; et al. (2010). "Mutations in GNA11 in uveal melanoma". N Engl J Med. 363 (23): 2191–9. doi:10.1056/NEJMoa1000584. PMC 3107972. PMID 21083380.
- ↑ 2.0 2.1 Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM; et al. (2009). "Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi". Nature. 457 (7229): 599–602. doi:10.1038/nature07586. PMC 2696133. PMID 19078957.
- ↑ 3.0 3.1 Shoushtari AN, Carvajal RD (2014). "GNAQ and GNA11 mutations in uveal melanoma". Melanoma Res. 24 (6): 525–34. doi:10.1097/CMR.0000000000000121. PMID 25304237.
- ↑ McGrath JJ (1986). "Nicotine and carbon monoxide: effects on the isolated rat heart". Alcohol. 3 (2): 157–60. PMID 3087380.
- ↑ Gupta MP, Lane AM, DeAngelis MM, Mayne K, Crabtree M, Gragoudas ES; et al. (2015). "Clinical Characteristics of Uveal Melanoma in Patients With Germline BAP1 Mutations". JAMA Ophthalmol. 133 (8): 881–7. doi:10.1001/jamaophthalmol.2015.1119. PMID 25974357.
- ↑ Harbour JW, Roberson ED, Anbunathan H, Onken MD, Worley LA, Bowcock AM (2013). "Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma". Nat Genet. 45 (2): 133–5. doi:10.1038/ng.2523. PMC 3789378. PMID 23313955.
- ↑ Fisher, M.; Kripke, M. (1982). "Suppressor T lymphocytes control the development of primary skin cancers in ultraviolet-irradiated mice". Science. 216 (4550): 1133–1134. doi:10.1126/science.6210958. ISSN 0036-8075.