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.

CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma

TURCHETTI, DANIELA;MICCOLI, SARA;
2016

Abstract

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.
CANCER LETTERS
Betti, M.; Aspesi, A.; Biasi, A.; Casalone, E.; Ferrante, D.; Ogliara, P.; Gironi, L.C.; Giorgione, R.; Farinelli, P.; Grosso, F.; Libener, R.; Rosato, S.; Turchetti, D.; Maffè, A.; Casadio, C.; Ascoli, V.; Dianzani, C.; Colombo, E.; Piccolini, E.; Pavesi, M.; Miccoli, S.; Mirabelli, D.; Bracco, C.; Righi, L.; Boldorini, R.; Papotti, M.; Matullo, G.; Magnani, C.; Pasini, B.; Dianzani, I.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/570098
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