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A multi-institutional study of the prevalence of BRCA1 and BRCA2 large genomic rearrangements in familial breast cancer patients

Moon-Woo Seong1, Sung Im Cho1, Kyu Hyung Kim2, Il Yong Chung3, Eunyoung Kang2, Jong Won Lee4, Sue K Park567, Min Hyuk Lee8, Doo Ho Choi9, Cha Kyong Yom10, Woo-Chul Noh11, Myung Chul Chang12, Sung Sup Park1, Sung-Won Kim2* and Korean Hereditary Breast Cancer Study Group

Author Affiliations

1 Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea

2 Department of Surgery, Seoul National University Bundang Hospital, Sungnam, Korea

3 Department of Surgery, National Medical Center, Seoul, Korea

4 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

5 Department of Preventive Medicine, Seoul National University College of medicine, Seoul, Korea

6 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea

7 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

8 Department of Surgery, Soonchunhyang University Hospital, Seoul, Korea

9 Department of Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea

10 Department of Surgery, Myongji Hospital, Goyang, Korea

11 Korea Institute of Radiological & Medical Sciences, Korea Cancer Center Hospital, Seoul, Korea

12 Department of Surgery, Dankook University Hospital, Cheonan, Korea

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BMC Cancer 2014, 14:645  doi:10.1186/1471-2407-14-645

Published: 1 September 2014



Large genomic rearrangements (LGRs) in the BRCA1/2 genes are frequently observed in breast cancer patients who are negative for BRCA1/2 small mutations. Here, we examined 221 familial breast cancer patients from 37 hospitals to estimate the contribution of LGRs, in a nationwide context, to the development of breast cancer.


Direct sequencing or mutation scanning followed by direct sequencing was performed to screen small mutations. BRCA1/2 small mutation-negative patients were screened for the presence of LGRs using a multiple ligation-dependent probe amplification (MLPA) assay.


Using a combined strategy to detect the presence of small mutations and LGRs, we identified BRCA1/2 small mutations in 78 (35.3%) out of 221 familial breast cancer patients and BRCA1 LGRs in 3 (2.1%) out of 143 BRCA1/2 small mutation-negative patients: the deletion of exons 11–13, the deletion of exons 13–15, and whole gene deletion of exons 1-24. The novel deletion of exons 11–13 is thought to result from a non-homologous recombination event mediated by a microhomology sequence comprised of 3 or 4 base pairs: c.3416_4357 + 1863delins187 (NG_005905.2: g.33369_44944delins187).


In this study, we showed that LGRs were found in 3.7% (3/81) of the patients who had mutations in BRCA1 or BRCA2, and 7.5% (3/40) of patients with mutations in BRCA1. This suggests that the contribution of LGRs to familial breast cancer in this population might be comparable to that in other ethnic populations. Given these findings, an MLPA to screen for mutations in the BRCA1 gene is recommended as an initial screening test in highly selective settings.

Breast cancer; Hereditary cancer; Large genomic rearrangement; BRCA1; BRCA2