Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas

Author:

Harbour J. William12,Onken Michael D.1,Roberson Elisha D. O.3,Duan Shenghui3,Cao Li3,Worley Lori A.1,Council M. Laurin3,Matatall Katie A.1,Helms Cynthia3,Bowcock Anne M.32

Affiliation:

1. Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.

2. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.

3. Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.

Abstract

An Eye on Metastasis Despite the considerable progress being made in elucidating the cell biology of metastasis, little is known about the genetic alterations that promote metastasis of human tumors, the cause of most cancer deaths. A potentially important clue now emerges from the work of Harbour et al. (p. 1410 , published online 4 November), who used an exome-sequencing approach to search for genetic mutations in uveal melanomas, an eye cancer associated with a high rate of fatal metastasis. Remarkably, over 80% of tumor samples with a high metastatic risk had inactivating somatic mutations in the gene encoding BAP1 (BRCA1-associated protein 1), a nuclear protein involved in controlling protein degradation. Thus, in this tumor type, mutational inactivation of BAP1 may be a key event in the acquisition of metastatic competence.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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