Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility

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Bibtex

@article{311569d9daa3433dbc0b18bc9ac0fd90,
title = "Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility",
abstract = "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.Genetics in Medicine advance online publication, 24 August 2017; doi:10.1038/gim.2017.123.",
author = "Irene Catucci and Ana Osorio and Brita Arver and Guido Neidhardt and Massimo Bogliolo and Federica Zanardi and Mirko Riboni and Simone Minardi and Roser Pujol and Jacopo Azzollini and Bernard Peissel and Siranoush Manoukian and {De Vecchi}, Giovanna and Stefano Casola and Jan Hauke and Lisa Richters and Kerstin Rhiem and Schmutzler, {Rita K} and Karin Wallander and Therese T{\"o}rngren and {\AA}ke Borg and Paolo Radice and Jordi Surrall{\'e}s and Eric Hahnen and Hans Ehrencrona and Anders Kvist and Javier Benitez and Paolo Peterlongo",
year = "2018",
doi = "10.1038/gim.2017.123",
language = "English",
volume = "20",
pages = "452–457",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams & Wilkins",

}