{Reference Type}: Journal Article
{Title}: Exome sequencing and case-control analyses identify RCC1 as a candidate breast cancer susceptibility gene.
{Author}: Riahi A;Radmanesh H;Schürmann P;Bogdanova N;Geffers R;Meddeb R;Kharrat M;Dörk T;
{Journal}: Int J Cancer
{Volume}: 142
{Issue}: 12
{Year}: 06 2018 15
{Factor}: 7.316
{DOI}: 10.1002/ijc.31273
{Abstract}: 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.