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01.09.2015 | Original Article

Heterozygous germline mutations in NBS1 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation

verfasst von: Haeyoung Kim, Dae-Yeon Cho, Doo Ho Choi, Gee Hue Jung, Inkyung Shin, Won Park, Seung Jae Huh, Sung-Won Kim, Sue K. Park, Jong Won Lee, Seok Jin Nam, Jeong Eon Lee, Won Ho Gil, Seok Won Kim

Erschienen in: Familial Cancer | Ausgabe 3/2015

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Abstract

The purpose of the present study was to analyze genetic variations in the NBS1 gene and to evaluate the contribution of heterozygous NBS1 mutation to the risk of breast cancer among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation. We screened 235 non-BRCA1/2 Korean patients with high-risk breast cancer for NBS1 mutations. The entire NBS1 gene was sequenced using fluorescent conformation-sensitive capillary electrophoresis. In silico analysis of the NBS1 variants was performed using PolyPhen-2 and SIFT. The frequency of variants predicted to be deleterious by in silico analysis was compared between breast cancer patients and controls. Twenty-eight sequence variants in the NBS1 gene were identified: 9 exonic variants, including 5 missense mutations (p.R169C, p.I171V, p.E185Q, p.E564K, and p.F603L) and 4 silent mutations, and 19 variants within introns. Among the five missense variants, p.I171V (c.511A > G) was the only variant predicted to be deleterious by in silico analysis. Heterozygosity for p.I171V was found in 4/235 patients with breast cancer and 3/281 individuals in the control group. The frequency of p.I171V was not significantly different between the patient and control groups (1.7 vs. 1.06 %, p = 0.7). Heterozygosity of p.I171V in the NBS1 gene was found in a small proportion of Korean patients with high-risk breast cancer. The contribution of the p.I171V variant to the development of breast cancer among Korean patients was not significant.

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Titel: Heterozygous germline mutations in NBS1 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation
verfasst von: Haeyoung Kim
Dae-Yeon Cho
Doo Ho Choi
Gee Hue Jung
Inkyung Shin
Won Park
Seung Jae Huh
Sung-Won Kim
Sue K. Park
Jong Won Lee
Seok Jin Nam
Jeong Eon Lee
Won Ho Gil
Seok Won Kim
Publikationsdatum: 01.09.2015
Verlag: Springer Netherlands
Erschienen in: Familial Cancer / Ausgabe 3/2015
Print ISSN: 1389-9600
Elektronische ISSN: 1573-7292
DOI: https://doi.org/10.1007/s10689-015-9789-9

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Heterozygous germline mutations in NBS1 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation

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