Individuals with FANCM biallelic mutations do no develop Fanconi anemia, but show risk for breast cancer, chemotherapy sensitivity toxicity and may display chromosome fragility
Catucci, Irene (Fondazione Italiana per la Ricerca sul Cancro)
Osorio, Ana (Centro Nacional de Investigaciones Oncológicas)
Arver, Brita (Karolinska Institutet (Estocolm, Suècia))
Neidhardt, Guido (Centrum für Integrierte Onkologie)
Bogliolo, Massimo (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Zanardi, Federica (Fondazione Italiana per la Ricerca sul Cancro)
Riboni, Mirko (Fondazione Italiana per la Ricerca sul Cancro)
Minardi, Simone (Fondazione Italiana per la Ricerca sul Cancro)
Pujol i Calvet, M. Roser (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Azzollini, Jacopo (Fondazione IRCCS Istituto Nazionale dei Tumori (Milà, Itàlia))
Peissel, Bernard (Fondazione IRCCS Istituto Nazionale dei Tumori (Milà, Itàlia))
Manoukian, Siranoush (Fondazione IRCCS Istituto Nazionale dei Tumori (Milà, Itàlia))
Vecchi, De, Giovanna (Fondazione Italiana per la Ricerca sul Cancro)
Casola, Stefano (Fondazione Italiana per la Ricerca sul Cancro)
Hauke, Jan (Universität zu Köln. Zentrum für Molekulare Medizin Köln)
Richters, Lisa (Universität zu Köln. Zentrum für Molekulare Medizin Köln)
Rhiem, Kerstin (Universität zu Köln. Zentrum für Molekulare Medizin Köln)
Schmutzler, Rita K. (Universität zu Köln. Zentrum für Molekulare Medizin Köln)
Wallander, Karin (Karolinska Institutet (Estocolm, Suècia))
Törngren, Therese (University of Lund. Department of Clinical Sciences)
Borg, Åke (University of Lund. Department of Clinical Sciences)
Radice, Paolo (Fondazione IRCCS Istituto Nazionale dei Tumori (Milà, Itàlia))
Surrallés i Calonge, Jordi (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Hahnen, Eric (Universität zu Köln. Zentrum für Molekulare Medizin Köln)
Ehrencrona, Hans (University of Lund. Department of Clinical Genetics)
Kvist, Anders (University of Lund. Department of Clinical Sciences)
Benitez, Javier (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Peterlongo, Paolo (Fondazione Italiana per la Ricerca sul Cancro)

Data:	2017
Resum:	PurposeMonoallelic germ-line mutations in the BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN genes confer high risk of breast cancer. Biallelic mutations in these genes cause Fanconi anemia (FA), characterized by malformations, bone marrow failure, chromosome fragility, and cancer predisposition (BRCA2/FANCD1 and PALB2/FANCN), or an FA-like disease presenting a phenotype similar to FA but without bone marrow failure (BRCA1/FANCS). FANCM monoallelic mutations have been reported as moderate risk factors for breast cancer, but there are no reports of any clinical phenotype observed in carriers of biallelic mutations. MethodsBreast cancer probands were subjected to mutation analysis by sequencing gene panels or testing DNA damage response genes. ResultsFive cases homozygous for FANCM loss-of-function mutations were identified. They show a heterogeneous phenotype including cancer predisposition, toxicity to chemotherapy, early menopause, and possibly chromosome fragility. Phenotype severity might correlate with mutation position in the gene. ConclusionOur data indicate that biallelic FANCM mutations do not cause classical FA, providing proof that FANCM is not a canonical FA gene. Moreover, our observations support previous findings suggesting that FANCM is a breast cancer-predisposing gene. Mutation testing of FANCM might be considered for individuals with the above-described clinical features.
Ajuts:	European Commission 703521 European Commission 305421 Ministerio de Economía y Competitividad SAF2015-64152-R Ministerio de Economía y Competitividad SAF2014-57680-R Ministerio de Economía y Competitividad CB06/07/0023
Nota:	Altres ajuts: MSSSI/FIS PI12/00070
Drets:	Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.
Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Publicat a:	Genetics in Medicine, Vol. 20 (April 2018) p. 452-457, ISSN 1098-3600

DOI: 10.1038/gim.2017.123

Post-print 21 p, 1.7 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats