Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas

被引：1059

作者：

Harbour, J. William ^{[1
,3
]}

Onken, Michael D. ^{[1
]}

Roberson, Elisha D. O. ^{[2
]}

Duan, Shenghui ^{[2
]}

Cao, Li ^{[2
]}

Worley, Lori A. ^{[1
]}

Council, M. Laurin ^{[2
]}

Matatall, Katie A. ^{[1
]}

Helms, Cynthia ^{[2
]}

Bowcock, Anne M. ^{[2
,3
]}

机构：

[1] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA

来源：

SCIENCE | 2010年 / 330卷 / 6009期

关键词：

UBIQUITIN HYDROLASE; BRCA1-ASSOCIATED PROTEIN-1; GNAQ; ASSOCIATION;

D O I：

10.1126/science.1194472

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1410 / 1413

页数：4