Haeyoung Kim1, Dae-Yeon Cho2, Doo Ho Choi3,4, Mijin Oh2, Inkyung Shin2, Won Park5, Seung Jae Huh5, Seok Jin Nam6, Jeong Eon Lee6, Seok Won Kim6. 1. Department of Radiation Oncology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea. hykim0131@daum.net. 2. LabGenomics Clinical Research Institute, LabGenomics, Seongnam, Republic of Korea. 3. Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. doho.choi@samsung.com. 4. Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Seoul, Republic of Korea. doho.choi@samsung.com. 5. Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 6. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Abstract
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 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. CONCLUSIONS: Pathogenic variants in CHEK2, PALB2, MRE11, and RAD50 were detected in a small proportion of Korean patients with features of 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 CHEK2c.1245dupC, PALB2 c.1048C>T, MRE11c.1773_1774delAA, RAD50 c.1276C>T, and RAD50c.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. CONCLUSIONS: Pathogenic variants in CHEK2, PALB2, MRE11, and RAD50 were detected in a small proportion of Korean patients with features of hereditary breast cancer.
Entities:
Keywords:
CHEK2; Hereditary breast and ovarian cancer syndrome; MRE11; PARB2; RAD50
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