Uveal melanoma pathophysiology: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 20: | Line 20: | ||
* These [[mutations]] lead to activation of downstream signaling pathways including the [[MAPK]] pathway in uveal melanoma. | * 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. | * 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.<ref name="pmid3087380">{{cite journal| author=McGrath JJ| title=Nicotine and carbon monoxide: effects on the isolated rat heart. | journal=Alcohol | year= 1986 | volume= 3 | issue= 2 | pages= 157-60 | pmid=3087380 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3087380 }} </ref> | * The [[mutations]] in the gene ''BAP1'' are strongly linked to metastatic spread and patient survival.<ref name="pmid3087380">{{cite journal| author=McGrath JJ| title=Nicotine and carbon monoxide: effects on the isolated rat heart. | journal=Alcohol | year= 1986 | volume= 3 | issue= 2 | pages= 157-60 | pmid=3087380 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3087380 }} </ref> | ||
* 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]].<ref name="pmid25974357">{{cite journal| author=Gupta MP, Lane AM, DeAngelis MM, Mayne K, Crabtree M, Gragoudas ES et al.| title=Clinical Characteristics of Uveal Melanoma in Patients With Germline BAP1 Mutations. | journal=JAMA Ophthalmol | year= 2015 | volume= 133 | issue= 8 | pages= 881-7 | pmid=25974357 | doi=10.1001/jamaophthalmol.2015.1119 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25974357 }} </ref> | * 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]].<ref name="pmid25974357">{{cite journal| author=Gupta MP, Lane AM, DeAngelis MM, Mayne K, Crabtree M, Gragoudas ES et al.| title=Clinical Characteristics of Uveal Melanoma in Patients With Germline BAP1 Mutations. | journal=JAMA Ophthalmol | year= 2015 | volume= 133 | issue= 8 | pages= 881-7 | pmid=25974357 | doi=10.1001/jamaophthalmol.2015.1119 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25974357 }} </ref> | ||
*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.<ref name="pmid23313955">{{cite journal| author=Harbour JW, Roberson ED, Anbunathan H, Onken MD, Worley LA, Bowcock AM| title=Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. | journal=Nat Genet | year= 2013 | volume= 45 | issue= 2 | pages= 133-5 | pmid=23313955 | doi=10.1038/ng.2523 | pmc=PMC3789378 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23313955 }} </ref> | *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.<ref name="pmid23313955">{{cite journal| author=Harbour JW, Roberson ED, Anbunathan H, Onken MD, Worley LA, Bowcock AM| title=Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. | journal=Nat Genet | year= 2013 | volume= 45 | issue= 2 | pages= 133-5 | pmid=23313955 | doi=10.1038/ng.2523 | pmc=PMC3789378 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23313955 }} </ref> | ||
| Line 34: | Line 34: | ||
== Microscopic Pathology == | == Microscopic Pathology == | ||
On microscopic histopathological analysis, | On microscopic histopathological analysis, we have 5 subtypes according to cell type into: Spindle A, spindle B, epitheliolid, mixed, and necrotic. | ||
<br /> | |||
==References== | ==References== | ||
Revision as of 12:06, 27 June 2019
|
Uveal melanoma Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Uveal melanoma pathophysiology On the Web |
|
American Roentgen Ray Society Images of Uveal melanoma pathophysiology |
|
Risk calculators and risk factors for Uveal melanoma pathophysiology |
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
- The exact pathogenesis of [disease name] is not completely understood.
OR
- It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
- [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
- Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
- [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
- The progression to [disease name] usually involves the [molecular pathway].
- The pathophysiology of [disease/malignancy] depends on the histological subtype.
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 [disease name] include:
- [Condition 1]
- [Condition 2]
- [Condition 3]
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.
References
- ↑ 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.
- ↑ 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.
- ↑ 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.