%0 Journal Article
%T Exome sequencing and case-control analyses identify RCC1 as a candidate breast cancer susceptibility gene.
%A Riahi A
%A Radmanesh H
%A Schürmann P
%A Bogdanova N
%A Geffers R
%A Meddeb R
%A Kharrat M
%A Dörk T
%J Int J Cancer
%V 142
%N 12
%D 06 2018 15
%M 29363114
%F 7.316
%R 10.1002/ijc.31273
%X Breast cancer is a genetic disease but the known genes explain a minority of cases. To elucidate the molecular basis of breast cancer in the Tunisian population, we performed exome sequencing on six BRCA1/BRCA2 mutation-negative patients with familial breast cancer and identified a novel frameshift mutation in RCC1, encoding the Regulator of Chromosome Condensation 1. Subsequent genotyping detected the 19-bp deletion in additional 5 out of 153 (3%) breast cancer patients but in none of 400 female controls (p = 0.0015). The deletion was enriched in patients with a positive family history (5%, p = 0.0009) and co-segregated with breast cancer in the initial pedigree. The mutant allele was lost in 4/6 breast tumors from mutation carriers which may be consistent with the hypothesis that RCC1 dysfunction provides a selective disadvantage at the stage of tumor progression. In summary, we propose RCC1 as a likely breast cancer susceptibility gene in the Tunisian population.