Frequency of pathogenic germline mutation in CHEK2, PALB2, MRE11, and RAD50 in patients at high risk for hereditary breast cancer

Purpose 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. Methods 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. Results 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 CHEK 2, 11 in PALB 2, 2 in MRE 11, 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. Conclusions Pathogenic variants in CHEK2 , PALB2 , MRE11 , and RAD50 were detected in a small proportion of Korean patients with features of hereditary breast cancer.