Frequent mutation of BAP1 in metastasizing uveal melanomas

J. William Harbour, Michael D. Onken, Elisha D.O. Roberson, Shenghui Duan, Li Cao, Lori A. Worley, M. Laurin Council, Katie A. Matatall, Cynthia Helms, Anne M. Bowcock

Research output: Contribution to journalArticlepeer-review

1139 Scopus citations


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.

Original languageEnglish
Pages (from-to)1410-1413
Number of pages4
Issue number6009
StatePublished - 3 Dec 2010
Externally publishedYes


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