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Published in: Journal of Translational Medicine 1/2012

Open Access 01-12-2012 | Research

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

Authors: Michele Carbone, Laura Korb Ferris, Francine Baumann, Andrea Napolitano, Christopher A Lum, Erin G Flores, Giovanni Gaudino, Amy Powers, Peter Bryant-Greenwood, Thomas Krausz, Elizabeth Hyjek, Rachael Tate, Joseph Friedberg, Tracey Weigel, Harvey I Pass, Haining Yang

Published in: Journal of Translational Medicine | Issue 1/2012

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Abstract

Background

BRCA1–associated protein 1 (BAP1) is a tumor suppressor gene located on chromosome 3p21. Germline BAP1 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 BAP1 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 BAP1 mutations and increased risk of malignant mesothelioma.

Methods

Suspicious cutaneous lesions were clinically and pathologically characterized and compared to those present in other families carrying BAP1 mutations. We then conducted a meta-analysis of all the studies reporting BAP1-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).

Results

Melanocytic tumors: of the five members of the L family studied, four (80%) carried a germline BAP1 mutation (p.Gln684*) and also presented one or more atypical melanocytic tumors; of the seven members of W family studied, all carried a germline BAP1 mutation (p.Pro147fs*48) and four of them (57%) presented one or more atypical melanocytic tumors, that we propose to call “melanocytic BAP1-mutated atypical intradermal tumors” (MBAITs). Meta-analysis: 118 individuals from seven unrelated families were selected and divided into a BAP1-mutated cohort and a BAP1-non-mutated cohort. Malignant mesothelioma, uveal melanoma, cutaneous melanoma, and MBAITs prevalence was significantly higher in the BAP1-mutated cohort (p ≤ 0.001).

Conclusions

Germline BAP1 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 BAP1 mutations and thus are at high risk of developing associated cancers.
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Metadata
Title
BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs
Authors
Michele Carbone
Laura Korb Ferris
Francine Baumann
Andrea Napolitano
Christopher A Lum
Erin G Flores
Giovanni Gaudino
Amy Powers
Peter Bryant-Greenwood
Thomas Krausz
Elizabeth Hyjek
Rachael Tate
Joseph Friedberg
Tracey Weigel
Harvey I Pass
Haining Yang
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-10-179

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