FaCD Online Syndrome Fact Sheet

Last updated: 30 Jan 2013

Name: Malignant Mesothelioma and Melanocytic Tumor syndrome, BAP1-associated

Mode of Inheritance: AD


BAP1, mapped to 3p21.1

Tumor features

lung/bronchial cancer
melanoma, cutaneous
melanoma, uveal (choroidal, ciliary body, iris)/ocular
mesothelioma, pleural

Tumor features (possible)

breast cancer
ovarian cancer (i.e. epithelial origin)
pancreatic adenocarcinoma
renal cell cancer, clear-cell (Grawitz tumor)


Somatic BAP1 mutations have been identified in several tumor types including mesothelioma, uveal melanoma, breast and lung cancer. Testa et al[1] identified germline BAP1 mutations in 2 families with a high incidence of malignant melanoma. They also identified 2 out of 26 patients with sporadic melanomas with such mutation; both also had developed uveal melanoma. Wiesner et al[2] reported two families with multiple papular skin-colored epitheloid melanocytic tumors. Numbers of tumors per individual ranged from 5 to over 50. A few cases of uveal melanoma and cutaneous melanoma were observed in these families. Additional uveal melanoma cases with BAP1 mutations have been reported[4]

Other tumors were observed in the reported families as well, but might have been coincidental[1]: premenopausal breast cancer, ovarian cancer, clear cell renal cancer, pancreatic cancer and leiomyosarcoma.Additional families have been reported, expanding the tumor spectrum with lung cancer and meningioma[3]


[1] Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011 Aug 28. [Epub ahead of print]
[2] Wiesner T, Obenauf AC, Murali R, Fried I, Griewank KG, Ulz P, Windpassinger C, Wackernagel W, Loy S, Wolf I, Viale A, Lash AE, Pirun M, Socci ND, Rütten A, Palmedo G, Abramson D, Offit K, Ott A, Becker JC, Cerroni L, Kutzner H, Bastian BC, Speicher MR. Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet. 2011 Aug 28.[Epub ahead of print]
[3] Abdel-Rahman MH, Pilarski R, Cebulla CM, Massengill JB, Christopher BN, Boru G, Hovland P, Davidorf FH. Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. J Med Genet. 2011 Sep 22. [Epub ahead of print]
[4] Höiom V, Edsgärd D, Helgadottir H, Eriksson H, All-Ericsson C, Tuominen R, Ivanova I, Lundeberg J, Emanuelsson O, Hansson J. Hereditary uveal melanoma: A report of a germline mutation in BAP1.Genes Chromosomes Cancer. 2013 Jan 23. doi: 10.1002/gcc.22035. [Epub ahead of print]