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

Journal of Translational Medicine

Research

Harvey I Pass¹  Elizabeth Hyjek²  Laura Korb Ferris³  Joseph Friedberg⁴  Tracey Weigel⁵  Rachael Tate⁶  Thomas Krausz⁷  Giovanni Gaudino⁸  Francine Baumann⁸  Erin G Flores⁸  Andrea Napolitano⁹  Christopher A Lum^1,10  Haining Yang^1,11  Michele Carbone^1,11  Amy Powers^1,12  Peter Bryant-Greenwood^1,12 

[1] Department of Cardiothoracic Surgery, New York University, NYU Langone Medical Center, 160 East 34th Street, 8th Floor, 10016, New York, NY, USA;Department of Pathology, The University of Chicago, 5841 S. Maryland Avenue, TW-055, 60637, Chicago, MC, IL, USA;Department of Pathology, University of Pittsburgh, Presby South Tower Suite, 3880 200 Lothrop Street, 15213, Pittsburgh, PA, USA;Department of Surgery, Penn Presbyterian Medical Center, 266 Wright Saunders Building, 39th & Market Streets, 19104, Philadelphia, PA, USA;Department of Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Clinical Science Center – H4, 53792-3284, Madison, WI, USA;Private Practice Physician, 1270 Attakapas Drive, 70570, Opelousas, LA, USA;The University of Chicago Medicine, 5841 S. Maryland Avenue, 60637, Chicago, IL, USA;University of Hawai‘i Cancer Center, 677 Ala Moana Boulevard, Suite 901, 96813, Honolulu, HI, USA;University of Hawai‘i Cancer Center, 677 Ala Moana Boulevard, Suite 901, 96813, Honolulu, HI, USA;Department of Molecular Biosciences and Bioengineering, University of Hawai‘i at Mānoa, 1955 East–west Road, Agricultural Science 218, 96822, Honolulu, HI, USA;University of Hawai‘i Cancer Center, 677 Ala Moana Boulevard, Suite 901, 96813, Honolulu, HI, USA;Department of Pathology, The Queen’s Medical Center, 1301 Punchbowl Street, 96813, Honolulu, HI, USA;University of Hawai‘i Cancer Center, 677 Ala Moana Boulevard, Suite 901, 96813, Honolulu, HI, USA;Pathology Department, University of Hawai‘i at Mānoa John. A. Burns School of Medicine, 651 Ilalo Street, MEB 401, 96813, Honolulu, HI, USA;University of Hawai‘i Cancer Center, 677 Ala Moana Boulevard, Suite 901, 96813, Honolulu, HI, USA;Pathology Department, University of Hawai‘i at Mānoa John. A. Burns School of Medicine, 651 Ilalo Street, MEB 401, 96813, Honolulu, HI, USA;Molecular Diagnostics and Biorepository, The Queen’s Medical Center, 1301 Punchbowl Street, 96813, Honolulu, HI, USA;

关键词: BAP1;    Mesothelioma;    Melanoma;    Cancer syndrome;    MBAITs;   

DOI  :  10.1186/1479-5876-10-179

 received in 2012-08-11, accepted in 2012-08-11,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundBRCA1–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.MethodsSuspicious 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).ResultsMelanocytic 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).ConclusionsGermline 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.

【 授权许可】

CC BY   
© Carbone et al.; licensee BioMed Central Ltd. 2012