Publication Date:
2010-11-06
Description:
Metastasis is a defining feature of malignant tumors and is the most common cause of cancer-related death, yet the genetics of metastasis are poorly understood. We used exome capture coupled with massively parallel sequencing to search for metastasis-related mutations in highly metastatic uveal melanomas of the eye. Inactivating somatic mutations were identified in the gene encoding BRCA1-associated protein 1 (BAP1) on chromosome 3p21.1 in 26 of 31 (84%) metastasizing tumors, including 15 mutations causing premature protein termination and 5 affecting its ubiquitin carboxyl-terminal hydrolase domain. One tumor harbored a frameshift mutation that was germline in origin, thus representing a susceptibility allele. These findings implicate loss of BAP1 in uveal melanoma metastasis and suggest that the BAP1 pathway may be a valuable therapeutic target.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087380/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087380/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harbour, J William -- Onken, Michael D -- Roberson, Elisha D O -- Duan, Shenghui -- Cao, Li -- Worley, Lori A -- Council, M Laurin -- Matatall, Katie A -- Helms, Cynthia -- Bowcock, Anne M -- AR007279-31A1/AR/NIAMS NIH HHS/ -- P30 EY02687C/EY/NEI NIH HHS/ -- R01 CA125970/CA/NCI NIH HHS/ -- R01 CA125970-06/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 3;330(6009):1410-3. doi: 10.1126/science.1194472. Epub 2010 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA. harbour@vision.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051595" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Line, Tumor
;
Chromosome Deletion
;
Chromosomes, Human, Pair 3/genetics
;
Frameshift Mutation
;
Germ-Line Mutation
;
Humans
;
Melanoma/*genetics/*secondary
;
*Mutation
;
Mutation, Missense
;
*Neoplasm Metastasis
;
Protein Structure, Tertiary
;
RNA Interference
;
RNA, Messenger/genetics/metabolism
;
RNA, Neoplasm/genetics/metabolism
;
Sequence Analysis, DNA
;
Tumor Suppressor Proteins/chemistry/*genetics/metabolism
;
Ubiquitin Thiolesterase/chemistry/*genetics/metabolism
;
Uveal Neoplasms/*genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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