CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma

被引：60

作者：

Betti, M. ^{[1
]}

Aspesi, A. ^{[1
]}

Biasi, A. ^{[1
]}

Casalone, E. ^{[2
,3
]}

Ferrante, D. ^{[4
,5
]}

Ogliara, P. ^{[6
]}

Gironi, L. C. ^{[7
]}

Giorgione, R. ^{[7
]}

Farinelli, P. ^{[7
]}

Grosso, F. ^{[8
]}

Libener, R. ^{[9
]}

Rosato, S. ^{[10
]}

Turchetti, D. ^{[11
]}

Maffe, A. ^{[12
]}

Casadio, C. ^{[13
]}

Ascoli, V. ^{[14
]}

Dianzani, C. ^{[15
]}

Colombo, E. ^{[7
]}

Piccolini, E. ^{[16
]}

Pavesi, M. ^{[17
]}

Miccoli, S. ^{[11
]}

Mirabelli, D. ^{[18
,19
,20
]}

Bracco, C. ^{[6
]}

Righi, L. ^{[21
]}

Boldorini, R. ^{[22
]}

Papotti, M. ^{[23
]}

Matullo, G. ^{[2
,3
]}

Magnani, C. ^{[4
,5
,20
]}

Pasini, B. ^{[2
,6
]}

Dianzani, I. ^{[1
,20
]}

机构：

[1] Univ Piemonte Orientate, Dept Hlth Sci, Novara, Italy

[2] Univ Turin, Dept Med Sci, Turin, Italy

[3] Human Genet Fdn, Turin, Italy

[4] Univ Piemonte Orientate, CPO Piemonte, Novara, Italy

[5] Univ Piemonte Orientate, Unit Med Stat & Epidemiol, Dept Translat Med, Novara, Italy

[6] AOU Citta Salute & Sci, Med Genet Unit, Turin, Italy

[7] Univ Piemonte Orientate, Dept Clin & Expt Med, Dermatol Clin, Novara, Italy

[8] SS Antonio & Biagio Gen Hosp, Div Med Oncol, Alessandria, Italy

[9] SS Antonio & Biagio Gen Hosp, Pathol Unit, Alessandria, Italy

[10] Arcispedale S Maria Nuova IRCCS, Clin Genet Sect, Dept Obstet Gynecol & Pediat, Reggio Emilia, Italy

[11] Policlin St Orsola Malpighi, Med Genet, Bologna, Italy

[12] Santa Croce & Carle Hosp, Mol Genet & Biol Unit, Cuneo, Italy

[13] Azienda Osped Univ Maggiore Carita, Thorac Surg Unit, Novara, Italy

[14] Univ Roma La Sapienza, Dept Radiol Oncol & Pathol Sci, Rome, Italy

[15] Univ Rome, Dept Dermatol, Campus Biomed, Rome, Italy

[16] Santo Spirito Hosp, Pneumol Unit, Casale Monferrato, Italy

[17] Santo Spirito Hosp, Anat Pathol Unit, Casale Monferrato, Italy

[18] CPO Piemonte, Unit Canc Epidemiol, Turin, Italy

[19] Univ Turin, Turin, Italy

[20] Univ Turin, Interdept Ctr Studies Asbestos & Other Tox Partic, Turin, Italy

[21] San Luigi Hosp, Univ Turin, Dept Oncol, Turin, Italy

[22] Univ Piemonte Orientate, Sect Pathol Anat, Dept Hlth Sci, Novara, Italy

[23] Univ Turin, AOU Citta Salute & Sci Torino, Dept Oncol, Turin, Italy

来源：

CANCER LETTERS | 2016年 / 378卷 / 02期

关键词：

Cancer predisposition syndrome; Asbestos exposure; Carcinogenesis; MALIGNANT PLEURAL MESOTHELIOMA; UVEAL MELANOMA; CLINICAL CHARACTERISTICS; CUTANEOUS MELANOMAS; FAMILY; CANCER; PATIENT; GENE; LUNG; SUSCEPTIBILITY;

D O I：

10.1016/j.canlet.2016.05.011

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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, MITE 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

引用

页码：120 / 130

页数：11

共 61 条

[1] Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers [J].