Back to Search Start Over

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

Authors :
Catucci, Irene
Osorio, Ana
Arver, Brita
Neidhardt, Guido
Bogliolo, Massimo
Zanardi, Federica
Riboni, Mirko
Minardi, Simone
Pujol, Roser
Azzollini, Jacopo
Peissel, Bernard
Manoukian, Siranoush
De Vecchi, Giovanna
Casola, Stefano
Hauke, Jan
Richters, Lisa
Rhiem, Kerstin
Schmutzler, Rita K
Wallander, Karin
Törngren, Therese
Borg, Åke
Radice, Paolo
Surrallés, Jordi
Hahnen, Eric
Ehrencrona, Hans
Kvist, Anders
Benitez, Javier
Peterlongo, Paolo
Source :
Genetics in Medicine; April 2018, Vol. 20 Issue: 4 p452-457, 6p
Publication Year :
2018

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.

Details

Language :
English
ISSN :
10983600 and 15300366
Volume :
20
Issue :
4
Database :
Supplemental Index
Journal :
Genetics in Medicine
Publication Type :
Periodical
Accession number :
ejs45317839
Full Text :
https://doi.org/10.1038/gim.2017.123