Alanazi Mohammad, Parine Narasimha Reddy, Shaik Jilani Purusottapatnam, Al Naeem Abdulrahman, Aldhaian Sooad
Genome Research Chair, Department of Biochemistry, College of Science King Saud, University, 11451 Riyadh, Saudi Arabia.
Basic Sciences Department, College of Science and Health Professions, King Saud bin, Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Saudi J Biol Sci. 2020 Oct;27(10):2651-2659. doi: 10.1016/j.sjbs.2020.05.047. Epub 2020 Jun 6.
Breast cancer is the most common cancer among women worldwide, causing 15% of cancer-related deaths among women. Breast cancer incidence rate is increasing in most countries. In Saudi Arabia, breast cancer constitutes nearly 22% of the newly diagnosed cancer cases in women. Breast cancer incidence in the women population of Saudi Arabia is 25.9%, with 18.2% mortality. In this study, targeted sequencing of 164 selected genes was performed on germline and somatic DNA derived from the blood and tissue samples of 50 breast cancer patients using customized panel on Ion torrent platform. This study focused on the identification of genetic variations of different cancer-causing genes, raising the hope for identification of personalized prognosis. After final filtration and validation, we found protein-truncating, non-synonymous missense, and splice site mutations in the known susceptibility genes for breast cancer. We identified a total of 14 point mutations and one deletion in , , and genes from the BRCA panel analysis of breast cancer samples. In the customized panel analysis, we identified 37 potential mutations in 25 breast cancer risk associated genes. Out of these, most mutations were observed in TP53. After filtration, we observed 7 mutations in TP53 genes (n = 7:- one stop gain (p.R81X), four non-synonymous (p.R81X, p.Y88C, p.R141H, and p.V25D), and two deletions (c.59delC and c.327delC)). Among the mutations detected in our study, TP53 (p.R81X), VHL (p.E52X), and (p.K3326X) mutations, which lead to an aberrant transcript with a premature stop codon, were reported for the first time in breast cancer patients from Saudi Arabia. Our study will help in identifying the damaging mutations and predisposing genes in Saudi breast cancer patients.
乳腺癌是全球女性中最常见的癌症，导致全球15%的女性癌症相关死亡。大多数国家的乳腺癌发病率都在上升。在沙特阿拉伯，乳腺癌占女性新诊断癌症病例的近22%。沙特阿拉伯女性人群中的乳腺癌发病率为25.9%，死亡率为18.2%。在本研究中，使用Ion torrent平台上的定制芯片，对50例乳腺癌患者血液和组织样本中的种系DNA和体细胞DNA进行了164个选定基因的靶向测序。本研究聚焦于不同致癌基因的遗传变异鉴定，为个性化预后的鉴定带来了希望。经过最终筛选和验证，我们在已知的乳腺癌易感基因中发现了蛋白质截短、非同义错义及剪接位点突变。通过对乳腺癌样本的BRCA芯片分析，我们在、和基因中总共鉴定出14个点突变和1个缺失。在定制芯片分析中，我们在25个乳腺癌风险相关基因中鉴定出37个潜在突变。其中，大多数突变发生在TP53基因中。筛选后，我们在TP53基因中观察到7个突变（n = 7：1个终止密码子获得突变（p.R81X）、4个非同义突变（p.R81X、p.Y88C、p.R141H和p.V25D）以及2个缺失（c.59delC和c.327delC））。在我们研究中检测到的突变中，TP53（p.R81X）、VHL（p.E52X）和（p.K3326X）突变导致转录本异常并带有提前终止密码子，这在沙特阿拉伯乳腺癌患者中属首次报道。我们的研究将有助于鉴定沙特乳腺癌患者中的有害突变和易感基因。
