Khoo Ui-Soon, Chan Kelvin Y K, Cheung Annie N Y, Xue W C, Shen D H, Fung K Y, Ngan Hextan Y S, Choy K W, Pang C P, Poon C S P, Poon A Y A, Ozcelik Hilmi
Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
Hum Mutat. 2002 Mar;19(3):307-8. doi: 10.1002/humu.9015.
Previous mutational analysis for BRCA gene mutations in sporadic ovarian cancer occurring in Chinese patients in Hong Kong identified six germline BRCA1 mutations and one germline BRCA2 mutation, six of which were novel (Khoo et al., 2000). Knowledge of BRCA gene mutations in the Chinese population is relatively scant. In this study, we focussed on whether any of these mutations could be recurrent in our Chinese population, making use of archival paraffin embedded tissue. A consecutive series of 214 ovarian cancer cases, half of Southern Chinese origin from Hong Kong whilst the other half of Northern Chinese origin from Beijing were used for the study. We identified one further novel mutation, 1081delG, in BRCA1. This was found to occur in two unrelated individuals with shared haplotype as revealed by allelotype analysis, thus demonstrating founder effect. Two other recurrent mutations were also identified, the 2371-2372delTG mutation in BRCA1 and the 3337C>T mutation in BRCA2 recurring in two and three unrelated individuals respectively, giving an overall prevalence 4.7% of recurrent BRCA mutations in ovarian cancer in the Southern Chinese population. Most importantly, all our recurrent mutation carriers were identified from Southern Chinese patients from Hong Kong whilst such mutations were absent in samples from the Northern Chinese. Our findings indicate possible heterogeneity in the BRCA genotype between Northern and Southern Chinese. The identification of a founder mutation and two recurrent mutations moreover, has important implications towards screening strategies for breast and ovarian cancer among Chinese of southern ancestral origin who are now dispersed throughout the world.
先前针对香港中国患者散发性卵巢癌中BRCA基因突变的突变分析，鉴定出6种种系BRCA1突变和1种种系BRCA2突变，其中6种是新突变（Khoo等人，2000年）。关于中国人群中BRCA基因突变的知识相对较少。在本研究中，我们利用存档的石蜡包埋组织，重点研究这些突变是否在中国人群中会反复出现。连续选取214例卵巢癌病例进行研究，其中一半来自香港的中国南方人，另一半来自北京的中国北方人。我们在BRCA1中又鉴定出一种新突变1081delG。通过等位基因分型分析发现，该突变发生在两个单倍型相同的无关个体中，从而证明了始祖效应。还鉴定出另外两种反复出现的突变，BRCA1中的2371 - 2372delTG突变和BRCA2中的3337C>T突变分别在两个和三个无关个体中反复出现，在中国南方人群的卵巢癌中，反复出现的BRCA突变总体患病率为4.7%。最重要的是，我们所有反复出现突变的携带者均来自香港的中国南方患者，而在中国北方患者的样本中未发现此类突变。我们的研究结果表明，中国北方人和南方人之间BRCA基因型可能存在异质性。此外，始祖突变和两种反复出现的突变的鉴定，对于筛查现在分散在世界各地的具有南方祖籍的中国人中的乳腺癌和卵巢癌的筛查策略具有重要意义。
