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Medline ® Abstract for Reference 53

of 'Inherited susceptibility to melanoma'

53
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Frequent mutation of BAP1 in metastasizing uveal melanomas.
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Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA, Council ML, Matatall KA, Helms C, Bowcock AM
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Science. 2010;330(6009):1410. Epub 2010 Nov 4.
 
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.
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Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA. harbour@vision.wustl.edu
PMID