title: Frequency of pathogenic germline mutation in CHEK2, PALB2, MRE11, and RAD50 in patients at high risk for hereditary breast cancer.
abstract: 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.
authors: Department of Radiation Oncology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea. hykim0131@daum.net.
authors: Haeyoung
authors: H
authors: Kim
authors: LabGenomics Clinical Research Institute, LabGenomics, Seongnam, Republic of Korea.
authors: Dae-Yeon
authors: DY
authors: Cho
authors: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. doho.choi@samsung.com.|Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Seoul, Republic of Korea. doho.choi@samsung.com.
authors: Doo Ho
authors: DH
authors: Choi
authors: LabGenomics Clinical Research Institute, LabGenomics, Seongnam, Republic of Korea.
authors: Mijin
authors: M
authors: Oh
authors: LabGenomics Clinical Research Institute, LabGenomics, Seongnam, Republic of Korea.
authors: Inkyung
authors: I
authors: Shin
authors: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Won
authors: W
authors: Park
authors: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Seung Jae
authors: SJ
authors: Huh
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Seok Jin
authors: SJ
authors: Nam
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Jeong Eon
authors: JE
authors: Lee
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Seok Won
authors: SW
authors: Kim
mesh_terms: D017766:Acid Anhydride Hydrolases; D000483:Alleles; D019943:Amino Acid Substitution; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D064447:Checkpoint Kinase 2 / Q000235:genetics*; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D000076164:Fanconi Anemia Complementation Group N Protein / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D000076228:MRE11 Homologue Protein / Q000235:genetics*; D059645:Mutation Rate; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000076164:Fanconi Anemia Complementation Group N Protein; C121766:MRE11 protein, human; D064447:Checkpoint Kinase 2; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes
keywords: CHEK2; Hereditary breast and ovarian cancer syndrome; MRE11; PARB2; RAD50