PerspectiveCANCER

Emerging Anatomy of the BAP1 Tumor Suppressor System

Science  21 Sep 2012:
Vol. 337, Issue 6101, pp. 1463-1464
DOI: 10.1126/science.1228463

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Summary

The genetic drivers of cancer are incredibly complex; they include frequent mutations in a small number of tumor suppressors and oncogenes, as well as a large landscape of rare genetic variants that may promote tumorigenesis in a lineage-dependent manner. A recent flurry of papers has demonstrated prevalent somatic and germline mutations in a novel tumor suppressor, the deubiquitinating enzyme BAP1, in a variety of tumor types, including some with metastatic potential (15). Through analysis of mice lacking BAP1 and human tumors, Dey et al. now identify BAP1 as a tumor suppressor in myelodysplastic syndrome (MDS), a bone marrow and blood cell cancer syndrome that often evolves into highly aggressive acute myelogenous leukemia (AML), as reported on page 1541 of this issue (6). Functional analysis of the BAP1 protein interaction network in vivo, together with target gene identification, revealed a transcription complex in which ubiquitin removal from regulatory components by BAP1 likely specifies the repertoire of genes underlying tumor suppression.