BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs
1 University of Hawai‘i Cancer Center, 677 Ala Moana Boulevard, Suite 901, Honolulu, 96813, HI, USA
2 Pathology Department, University of Hawai‘i at Mānoa John. A. Burns School of Medicine, 651 Ilalo Street, MEB 401, Honolulu, 96813, HI, USA
3 Department of Molecular Biosciences and Bioengineering, University of Hawai‘i at Mānoa, 1955 East–west Road, Agricultural Science 218, Honolulu, 96822, HI, USA
4 Department of Pathology, The Queen’s Medical Center, 1301 Punchbowl Street, Honolulu, HI, 96813, USA
5 Molecular Diagnostics and Biorepository, The Queen’s Medical Center, 1301 Punchbowl Street, Honolulu, 96813, HI, USA
6 Department of Pathology, University of Pittsburgh, Presby South Tower Suite, 3880 200 Lothrop Street, Pittsburgh, 15213, PA, USA
7 The University of Chicago Medicine, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA
8 Department of Pathology, The University of Chicago, 5841 S. Maryland Avenue, Chicago, TW-055, MC, IL, 60637, USA
9 Private Practice Physician, 1270 Attakapas Drive, Opelousas, 70570, LA, USA
10 Department of Surgery, Penn Presbyterian Medical Center, 266 Wright Saunders Building, 39th & Market Streets, Philadelphia, 19104, PA, USA
11 Department of Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Clinical Science Center – H4, Madison, 53792-3284, WI, USA
12 Department of Cardiothoracic Surgery, New York University, NYU Langone Medical Center, 160 East 34th Street, 8th Floor, New York, 10016, NY, USA
Journal of Translational Medicine 2012, 10:179 doi:10.1186/1479-5876-10-179Published: 30 August 2012
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.
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).
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).
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.