Amemiya Yutaka, Bacopulos Stephanie, Al-Shawarby Mohamed, Al-Tamimi Dalal, Naser Walid, Ahmed Ayesha, Khalifa Mahmoud, Slodkowska Elzbieta, Seth Arun
Genomics Core Facility, Toronto, ON, Canada Sunnybrook Research Institute, Toronto, ON, Canada.
Sunnybrook Research Institute, Toronto, ON, Canada.
Anticancer Res. 2015 May;35(5):2601-10.
Previous reports have indicated that patients with breast cancer who are from the Eastern Province of Saudi Arabia have a different gene expression profile from that known for their age-matched North American population. In the present study, breast tumor samples from Canadian and Saudi Arabian patients were screened for known and unknown mutations within BRCA1 and BRCA2 as well as 21 additional genes, including, ATM, BARD1, CDH1, P53, EPCAM, MSH6, and RAD50, which have been implicated in breast and ovarian cancer predisposition. A total of 129 non-synonymous mutations were identified by Ion Torrent amplicon sequencing. Forty-one mutations in 18 genes were unique to the Canadian population and 59 mutations in 20 genes were unique to the Saudi Arabian population. A total of 55/129 unique mutations in 22 genes were not previously reported in the database. Twenty-nine mutations in 16 genes were common to both populations; one of these mutations was not previously reported in the database. The most frequently mutated gene in both populations was the BRCA2 gene, followed by BRCA1 and TP53. Unique to this work is the identification of mutations frequently found in the Saudi Arabian population that are rare in the Canadian population. This work will allow direction of genetic analysis resources toward the clinical needs of each particular population.
先前的报告表明，来自沙特阿拉伯东部省份的乳腺癌患者具有与年龄匹配的北美人群不同的基因表达谱。在本研究中，对加拿大和沙特阿拉伯患者的乳腺肿瘤样本进行了筛查，以检测BRCA1和BRCA2以及另外21个基因（包括ATM、BARD1、CDH1、P53、EPCAM、MSH6和RAD50）中的已知和未知突变，这些基因与乳腺癌和卵巢癌易感性有关。通过Ion Torrent扩增子测序共鉴定出129个非同义突变。18个基因中的41个突变是加拿大人群特有的，20个基因中的59个突变是沙特阿拉伯人群特有的。22个基因中的55/129个独特突变此前未在数据库中报道。16个基因中的29个突变在两个群体中都很常见；其中一个突变此前未在数据库中报道。两个群体中最常发生突变的基因是BRCA2基因，其次是BRCA1和TP53。这项工作的独特之处在于鉴定出在沙特阿拉伯人群中经常发现但在加拿大人群中罕见的突变。这项工作将使遗传分析资源能够针对每个特定人群的临床需求。
