Frequency of pathogenic germline mutation in CHEK2, PALB2, MRE11, and RAD50 in patients at high risk for hereditary breast cancer
Frequency of pathogenic germline mutation in CHEK2, PALB2, MRE11, and RAD50 in patients at high risk for hereditary breast cancer
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DOI：
10.1007/s10549-016-4034-2
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发表时间：
2017-01-01
影响因子：
3.8
通讯作者：
Kim, Seok Won
中科院分区：
文献类型：
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作者：
Kim, Haeyoung;Cho, Dae-Yeon;Kim, Seok Won
本研究旨在评估韩国遗传性乳腺癌高危患者CHEK 2、PALB 2、MRE 11和RAD 50基因突变的频率，共纳入235例BRCA 1/2突变阴性的韩国遗传性乳腺癌患者。使用大规模平行测序（MPS）分析CHEK 2、PALB 2、MRE 11和RAD 50的整个编码区。MPS检测到的序列变异经桑格测序证实，其中CHEK 2（n = 1）、PALB 2（n = 2）、MRE 11（n = 1）和RAD 50（n = 2）致病性变异6例（2.5%）。在致病性变体中，PALB 2 c.2257C > T先前在其他研究中报道，而CHEK 2 c.1245dupC、PALB 2 c.1048C > T、MRE 11 c.1773_1774delAA、RAD 50 c.1276C > T和RAD 50 c.3811_3813delGAA在本研究中新鉴定。在26名患者中，在4个基因中共发现15个错义变异; 7名患者在CHEK 2中有一个变异，PALB 2中有11个，MRE 11中有2个，RAD 50中有6个。当对15种错义变体进行计算机模拟分析时，预测CHEK 2、PALB 2 c.1492G > T、PALB 2 c.3054G > C、MRE 11 c.140C > T、RAD 50 c.1456C > T和RAD 50 c.3790C > T中的致病性变体是有害的。和RAD 50在一小部分具有遗传性乳腺癌特征的韩国患者中检测到。
This study was performed to evaluate the frequency of mutations in CHEK2, PALB2, MRE11, and RAD50 among Korean patients at high risk for hereditary breast cancer.A total of 235 Korean patients with hereditary breast cancer who tested negative for BRCA1/2 mutation were enrolled to this study. Entire coding regions of CHEK2, PALB2, MRE11, and RAD50 were analyzed using massively parallel sequencing (MPS). Sequence variants detected by MPS were confirmed by Sanger sequencing.Six patients (2.5 %) were found to have pathogenic variants in CHEK2 (n = 1), PALB2 (n = 2), MRE11 (n = 1), and RAD50 (n = 2). Among the pathogenic variants, PALB2 c.2257C > T was previously reported in other studies, while CHEK2 c.1245dupC, PALB2 c.1048C > T, MRE11 c.1773_1774delAA, RAD50 c.1276C > T, and RAD50 c.3811_3813delGAA were newly identified in this study. A total of 15 missense variants were found in the four genes among 26 patients; 7 patients had a variant in CHEK2, 11 in PALB2, 2 in MRE11, and 6 in RAD50. When in silico analyses were performed to the 15 missense variants, six variants (CHEK2 c.686A > G, PALB2 c.1492G > T, PALB2 c.3054G > C, MRE11 c.140C > T, RAD50 c.1456C > T, and RAD50 c.3790C > T) were predicted to be deleterious.Pathogenic variants in CHEK2, PALB2, MRE11, and RAD50 were detected in a small proportion of Korean patients with features of hereditary breast cancer.