Title |
Identification of large genomic rearrangement of BRCA1/2 in high risk patients in Korea
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Published in |
BMC Medical Genomics, March 2017
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DOI | 10.1186/s12881-017-0398-3 |
Pubmed ID | |
Authors |
Do-Hoon Kim, Hyojin Chae, Irene Jo, Jaeeun Yoo, Hyeyoung Lee, Woori Jang, Joonhong Park, Gun Dong Lee, Dong-Seok Jeon, Keun Ho Lee, Soo Young Hur, Byung Joo Chae, Byung Joo Song, Myungshin Kim, Yonggoo Kim |
Abstract |
While the majority of germline inactivating mutations in BRCA1/2 are small-scale mutations, large genomic rearrangements (LGRs) are also detected in a variable proportion of patients. However, routine genetic methods are incapable of detecting LGRs, and comprehensive genetic testing algorithm is necessary. We performed multiplex ligation-dependent probe amplification assay for small-scale mutation negative patients at high-risk for LGR, based on previously published LGR risk criteria. The inclusion criteria for the high-risk subgroup were personal history of 1) early-onset breast cancer (diagnosed at ≤36 years); 2) two breast primaries; 3) breast cancer diagnosed at any age, with ≥1 close blood relatives (includes first-, second-, or third-degree) with breast and/or epithelial ovarian cancer; 4) both breast and epithelial ovarian cancer diagnosed at any age; and 5) epithelial ovarian cancer with ≥1 close blood relatives with breast and/or epithelial ovarian cancer. Two LGRs were identified. One was a heterozygous deletion of exon 19 and the other was a heterozygous duplication of exon 4-6. The prevalence of LGRs was 7% among Sanger-negative, high-risk patients, and accounted for 13% of all BRCA1 mutations and 2% of all patients. Moreover, LGRs reported in Korean patients, including our 2 newly identified cases, were found exclusively in families with at least one high-risk feature. Our result suggests that selective LGR screening for Sanger-negative, high-risk patients is necessary for Korean patients. |
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Student > Master | 3 | 17% |
Researcher | 2 | 11% |
Professor | 2 | 11% |
Other | 1 | 6% |
Student > Doctoral Student | 1 | 6% |
Other | 2 | 11% |
Unknown | 7 | 39% |
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Medicine and Dentistry | 3 | 17% |
Agricultural and Biological Sciences | 1 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 6% |
Unknown | 7 | 39% |