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DNA repair genes implicated in triple negative familial non-BRCA1/2 breast cancer predisposition.


ABSTRACT: Among breast cancers, 10 to 15% of cases would be due to hereditary risk. In these familial cases, mutations in BRCA1 and BRCA2 are found in only 15% to 20%, meaning that new susceptibility genes remain to be found. Triple-negative breast cancers represent 15% of all breast cancers, and are generally aggressive tumours without targeted therapies available. Our hypothesis is that some patients with triple negative breast cancer could share a genetic susceptibility different from other types of breast cancers. We screened 36 candidate genes, using pyrosequencing, in all the 50 triple negative breast cancer patients with familial history of cancer but no BRCA1 or BRCA2 mutation of a population of 3000 families who had consulted for a familial breast cancer between 2005 and 2013. Any mutations were also sequenced in available relatives of cases. Protein expression and loss of heterozygosity were explored in tumours. Seven deleterious mutations in 6 different genes (RAD51D, MRE11A, CHEK2, MLH1, MSH6, PALB2) were observed in one patient each, except the RAD51D mutation found in two cases. Loss of heterozygosity in the tumour was found for 2 of the 7 mutations. Protein expression was absent in tumour tissue for 5 mutations. Taking into consideration a specific subtype of tumour has revealed susceptibility genes, most of them in the homologous recombination DNA repair pathway. This may provide new possibilities for targeted therapies, along with better screening and care of patients.

SUBMITTER: Ollier M 

PROVIDER: S-EPMC4548324 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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DNA repair genes implicated in triple negative familial non-BRCA1/2 breast cancer predisposition.

Ollier Marie M   Radosevic-Robin Nina N   Kwiatkowski Fabrice F   Ponelle Flora F   Viala Sandrine S   Privat Maud M   Uhrhammer Nancy N   Bernard-Gallon Dominique D   Penault-Llorca Frédérique F   Bignon Yves-Jean YJ   Bidet Yannick Y  

American journal of cancer research 20150615 7


Among breast cancers, 10 to 15% of cases would be due to hereditary risk. In these familial cases, mutations in BRCA1 and BRCA2 are found in only 15% to 20%, meaning that new susceptibility genes remain to be found. Triple-negative breast cancers represent 15% of all breast cancers, and are generally aggressive tumours without targeted therapies available. Our hypothesis is that some patients with triple negative breast cancer could share a genetic susceptibility different from other types of br  ...[more]

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