Park Boyoung, Sohn Ji Yeon, Yoon Kyong-Ah, Lee Keun Seok, Cho Eun Hae, Lim Myong Cheol, Yang Moon Jung, Park Soo Jin, Lee Moo Hyun, Lee See Youn, Chang Yoon Jung, Lee Dong Ock, Kong Sun-Young, Lee Eun Sook
Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-Si, Gyeonggi-do, 10408, Korea.
National Cancer Control Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-Si, Gyeonggi-do, 10408, Korea.
Breast Cancer Res Treat. 2017 May;163(1):139-150. doi: 10.1007/s10549-017-4142-7. Epub 2017 Feb 15.
We investigated the prevalence of BRCA1/2 small mutations and large genomic rearrangements in high risk breast cancer patients who attended a genetic counseling clinic.
In total 478 patients were assessed for BRCA1/2 mutations by direct sequencing, of whom, 306 were identified as non-carriers of BRCA1/2 mutation and assessed for large rearrangement mutations by multiplex ligation-dependent probe amplification. Family history and clinicopathological characteristics of patients were evaluated.
Sixty-three mutation carriers (13.2%) were identified with BRCA1 mutations (6.3%) and BRCA2 mutations (6.9%), respectively. Mutation frequency was affected by familial and personal factors. Breast cancer patients with family history of breast and ovarian cancer showed the highest prevalence of BRCA1/2 mutations (67%), and triple-negative breast cancer (TNBC) patients showed high BRCA1 mutation prevalence (25%). The three probands of BRCA1 deletion (1%) represented both familial risk and personal or clinicopathological risk factors as two with TNBC and one with bilateral ovarian cancer.
This is the largest study assessing large genomic rearrangement prevalence in Korea and BRCA1 deletion frequency was low as 1% in patients without BRCA1/2 small mutations. For clinical utility of large genomic rearrangement testing needs further study.
我们调查了在一家遗传咨询诊所就诊的高危乳腺癌患者中BRCA1/2小突变和大基因组重排的发生率。
总共478例患者通过直接测序评估BRCA1/2突变，其中306例被鉴定为BRCA1/2突变非携带者，并通过多重连接依赖探针扩增评估大重排突变。评估患者的家族史和临床病理特征。
共鉴定出63例突变携带者（13.2%），分别携带BRCA1突变（6.3%）和BRCA2突变（6.9%）。突变频率受家族和个人因素影响。有乳腺癌和卵巢癌家族史的乳腺癌患者BRCA1/2突变发生率最高（67%），三阴性乳腺癌（TNBC）患者BRCA1突变发生率较高（25%）。BRCA1缺失的3例先证者（1%）既代表家族风险，也代表个人或临床病理风险因素，其中2例为TNBC，1例为双侧卵巢癌。
这是韩国评估大基因组重排发生率的最大规模研究，在无BRCA1/2小突变的患者中，BRCA1缺失频率低至1%。大基因组重排检测的临床实用性需要进一步研究。
