BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs

• Main Authors: Carbone Michele, Ferris Laura, Baumann Francine, Napolitano Andrea, Lum Christopher A, Flores Erin G, Gaudino Giovanni, Powers Amy, Bryant-Greenwood Peter, Krausz Thomas, Hyjek Elizabeth, Tate Rachael, Friedberg Joseph, Weigel Tracey, Pass Harvey I, Yang Haining
• Format: Article
• Language: English
• Published: BMC 2012-08-01
• Series: Journal of Translational Medicine
• Subjects: BAP1; Mesothelioma; Melanoma; Cancer syndrome; MBAITs
• Online Access: http://www.translational-medicine.com/content/10/1/179
• ISSN: 1479-5876

<p>Abstract</p> <p>Background</p> <p>BRCA1–associated protein 1 (<it>BAP1</it>) is a tumor suppressor gene located on chromosome 3p21. Germline <it>BAP1</it> mutations have been recently associated with an increased risk of malignant mesothelioma, atypical melanocytic tumors and other neoplasms. To answer the question if different germline <it>BAP1</it> mutations may predispose to a single syndrome with a wide phenotypic range or to distinct syndromes, we investigated the presence of melanocytic tumors in two unrelated families (L and W) with germline <it>BAP1</it> mutations and increased risk of malignant mesothelioma.</p> <p>Methods</p> <p>Suspicious cutaneous lesions were clinically and pathologically characterized and compared to those present in other families carrying <it>BAP1</it> mutations. We then conducted a meta-analysis of all the studies reporting <it>BAP1</it>-mutated families to survey cancer risk related to the germline BAP1 mutation (means were compared using t-test and proportions were compared with Pearson χ² test or two-tailed Fisher’s exact test).</p> <p>Results</p> <p>Melanocytic tumors: of the five members of the L family studied, four (80%) carried a germline <it>BAP1</it> mutation (p.Gln684*) and also presented one or more atypical melanocytic tumors; of the seven members of W family studied, all carried a germline <it>BAP1</it> mutation (p.Pro147fs*48) and four of them (57%) presented one or more atypical melanocytic tumors, that we propose to call “melanocytic <it>BAP1</it>-mutated atypical intradermal tumors” (MBAITs). Meta-analysis: 118 individuals from seven unrelated families were selected and divided into a <it>BAP1</it>-mutated cohort and a <it>BAP1</it>-non-mutated cohort. Malignant mesothelioma, uveal melanoma, cutaneous melanoma, and MBAITs prevalence was significantly higher in the <it>BAP1</it>-mutated cohort (p ≤ 0.001).</p> <p>Conclusions</p> <p>Germline <it>BAP1</it> mutations are associated with a novel cancer syndrome characterized by malignant mesothelioma, uveal melanoma, cutaneous melanoma and MBAITs, and possibly by other cancers. MBAITs provide physicians with a marker to identify individuals who may carry germline <it>BAP1</it> mutations and thus are at high risk of developing associated cancers.</p>