Exome sequencing and case–control analyses identify RCC1 as a candidate breast cancer susceptibility gene

Riahi, A. and Radmanesh, H. and Schürmann, P. and Bogdanova, N. and Geffers, R. and Meddeb, R. and Kharrat, M. and Dörk, T. (2018) Exome sequencing and case–control analyses identify RCC1 as a candidate breast cancer susceptibility gene. International Journal of Cancer, 142 (12). pp. 2512-2517.

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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. © 2018 UICC

Item Type: Article
Additional Information: Cited By :1 Export Date: 16 February 2020 CODEN: IJCNA Correspondence Address: Dörk, T.; Gynaecology Research Unit, Hannover Medical SchoolGermany; email: doerk.thilo@mh-hannover.de
Uncontrolled Keywords: breast carcinoma founder mutation mitosis RCC1 replication adult age distribution aged allele Article breast cancer cancer staging cancer susceptibility case control study chromosome condensation controlled study familial disease female frameshift mutation gene deletion genetic identification genetic susceptibility genotype human major clinical study middle aged oncogene priority journal RCC1 gene tumor growth Tunisian whole exome sequencing breast tumor exome genetic association study genetic predisposition genetics pedigree Tunisia very elderly cell cycle protein guanine nucleotide exchange factor nuclear protein RCC1 protein, human Aged, 80 and over Breast Neoplasms Case-Control Studies Cell Cycle Proteins Genetic Association Studies Genetic Predisposition to Disease Guanine Nucleotide Exchange Factors Humans Nuclear Proteins
Subjects: WP Gynecology
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 06 May 2020 12:33
Last Modified: 06 May 2020 12:33
URI: http://eprints.mums.ac.ir/id/eprint/17492

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