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The genetics of uveal melanoma: an emerging framework for targeted therapy.
Pigment Cell Melanoma Res. 2012 Mar; 25(2):171-81
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19 Mar 2012
Review / Commentary
DOI: 10.3410/f.14021971.15478074
This article is a great review of all genetic findings in uveal melanoma over the past two decades. The author explains and describes the chromosomal alterations, molecular pathways, GNAQ and GNA11 mutations, gene expression profile and microRNA expression in uveal melanoma. The author also compares the...Continue reading
This article is a great review of all genetic findings in uveal melanoma over the past two decades. The author explains and describes the chromosomal alterations, molecular pathways, GNAQ and GNA11 mutations, gene expression profile and microRNA expression in uveal melanoma. The author also compares the genetic similarities and differences between uveal and cutaneous melanoma.
The author begins by showing that what was known in the past decades regarding the clinical/histopathological features associated with worse or better prognosis for uveal melanoma metastasis remains unchanged. However, in the recent years the efforts to better understand the molecular changes in uveal melanoma have shown different potential molecular targets and have provided an unprecedented opportunity for targeted therapy of metastatic disease. This review is a tremendous opportunity to be updated in the progress that has been made in the ocular oncology field. For further reading, see {1-7}.
The author begins by showing that what was known in the past decades regarding the clinical/histopathological features associated with worse or better prognosis for uveal melanoma metastasis remains unchanged. However, in the recent years the efforts to better understand the molecular changes in uveal melanoma have shown different potential molecular targets and have provided an unprecedented opportunity for targeted therapy of metastatic disease. This review is a tremendous opportunity to be updated in the progress that has been made in the ocular oncology field. For further reading, see {1-7}.
References
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Prognostic biomarkers in uveal melanoma: evidence for a stem cell-like phenotype associated with metastasis.
Melanoma Res 2008 Jun; 3(18):191-200
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Loss of heterozygosity of chromosome 3 detected with single nucleotide polymorphisms is superior to monosomy 3 for predicting metastasis in uveal melanoma.
Clin Cancer Res 2007 May 15; 10(13):2923-7
PMID: 17504992
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Oncogenic mutations in GNAQ occur early in uveal melanoma.
Invest Ophthalmol Vis Sci 2008 Dec; 12(49):5230-4
PMID: 18719078
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An accurate, clinically feasible multi-gene expression assay for predicting metastasis in uveal melanoma.
J Mol Diagn 2010 Jul; 4(12):461-8
PMID: 20413675
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Frequent mutation of BAP1 in metastasizing uveal melanomas.
Science 2010 Dec 3; 6009(330):1410-3
PMID: 21051595
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Germline mutations in BAP1 predispose to melanocytic tumors.
Nat Genet 2011 Oct; 10(43):1018-21
PMID: 21874003
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Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma.
Clin Cancer Res 2012 Jan 15; 2(18):408-16
PMID: 22038994
Disclosures
None declared
Add Comment
Materin M and Simões C: F1000Prime Recommendation of [Harbour JW, Pigment Cell Melanoma Res 2012, 25(2):171-81]. In F1000Prime, 19 Mar 2012; DOI: 10.3410/f.14021971.15478074. F1000Prime.com/14021971#eval15478074
F1000Prime Recommendations, Dissents and Comments for [Harbour JW, Pigment Cell Melanoma Res 2012, 25(2):171-81]. In F1000Prime, 21 May 2013; F1000Prime.com/14021971
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Uveal melanoma is the second most common form of melanoma and the most common primary intraocular malignancy. Until recently, very little was known about the genetics of this aggressive cancer. Mutations in oncogenes and tumor suppressors that are common in other cancers are conspicuously absent in uveal melanoma. In recent years, however, uveal melanoma has begun to yield its secrets, and a fascinating picture is emerging of how it develops and progresses. Mutations in the G(q) alpha subunits, encoded by GNAQ and GNA11, appear to be early or perhaps initiating events that require further mutations for malignant transformation. On the other hand, mutations in the BRCA1-associated protein-1 (BAP1) appear to occur later and demarcate a molecular brink beyond which metastasis becomes highly likely. BAP1 mutations can also occur in the germline, leading to a distinctive cancer predisposition syndrome. These mutations appear to be key events that provide the potential for targeted therapy. This article will review the genetic findings in uveal melanoma over the past two decades and suggest important areas for future work.
© 2012 John Wiley & Sons A/S.
DOI: 10.1111/j.1755-148X.2012.00979.x
PMID: 22268848
