CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma

M. Betti, Anna Aspesi, Alessandra Biasi, Elisabetta Casalone, D. Ferrante, Paola Ogliara, L. C. Gironi, R. Giorgione, P. Farinelli, F. Grosso, R. Libener, S. Rosato, Daniela Turchetti, Antonella Maffè, C. Casadio, V. Ascoli, Chiara Dianzani, E. Colombo, E. Piccolini, M. PavesiSara Miccoli, Dario Mirabelli, C. Bracco, L. Righi, Renzo Boldorini, M. Papotti, G. Matullo, C. Magnani, Barbara Pasini, I. Dianzani

Research output: Contribution to journalArticlepeer-review


BAP1 germline mutations predispose to a cancer predisposition syndrome that includes mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for BAP1 and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. In two out of six families with both mesothelioma and melanoma we identified either a germline nonsense mutation (c.1153C > T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation (c.301G > T, p.Gly101Trp) in CDKN2A. Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that these tumors share key steps that drive carcinogenesis and that other genes may be involved in inherited predisposition to malignant mesothelioma and melanoma.

Original languageEnglish
Pages (from-to)120-130
Number of pages11
JournalCancer Letters
Issue number2
Publication statusPublished - Aug 10 2016


  • Asbestos exposure
  • Cancer predisposition syndrome
  • Carcinogenesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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