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

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Abstract

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
JournalScience
Volume330
Issue number6009
DOIs
StatePublished - Dec 3 2010
Externally publishedYes

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William Harbour, J., Onken, M. D., Roberson, E. D. O., Duan, S., Cao, L., Worley, L. A., Council, M. L., Matatall, K. A., Helms, C., & Bowcock, A. M. (2010). Frequent mutation of BAP1 in metastasizing uveal melanomas. Science, 330(6009), 1410-1413. https://doi.org/10.1126/science.1194472