Baig Ruqia Mehmood, Mahjabeen Ishrat, Sabir Maimoona, Masood Nosheen, Hafeez Saniya, Malik Faraz Arshad, Kayani Mahmood Akhtar
Cancer Genetics Lab, COMSATS Institute of Information and Technology, Islamabad, Pakistan.
Asian Pac J Cancer Prev. 2011;12(10):2773-8.
The PTEN gene, a candidate tumor suppressor, is one of the more commonly inactivated and extensively studied genes in cancer. However, few data are available about the role of germ line mutations of this gene in sporadic breast cancer cases. The purpose of this study was to determine extent of involvement of this gene in breast cancer in Pakistan. To test the hypothesis that genetic variations of PTEN play a role in the etiology of breast cancer, a population based case-control study was conducted in 350 breast cancer patients along 400 healthy controls. After extracting DNA from blood, the whole coding sequence of PTEN along with intron/exon boundaries was genotyped by polymerase chain reaction-single stranded conformational polymorphism. Sequencing analysis revealed nineteen different types of mutations in different regions of PTEN (in exon 2, 4, 5, 6, 7 and splicing sites of intron 2 and 4 and also in the 3' UTR region), including 3 silent, 8 missense, 2 frame shift and 6 splice site variations. Among the observed variations in this study, three missense mutations have already been reported i.e. 319G>A (Asp106Asn), 389G>A (Arg129Gln) and 482G>A (Arg160Lys) in different populations. The present results suggest that a wide range of germline PTEN mutations may play a role in the pathogenesis of breast cancer.
PTEN基因是一种候选肿瘤抑制基因，是癌症中较常失活且研究广泛的基因之一。然而，关于该基因种系突变在散发性乳腺癌病例中的作用，可用数据很少。本研究的目的是确定该基因在巴基斯坦乳腺癌中的受累程度。为了检验PTEN基因变异在乳腺癌病因中起作用的假设，对350例乳腺癌患者和400例健康对照进行了一项基于人群的病例对照研究。从血液中提取DNA后，通过聚合酶链反应-单链构象多态性对PTEN的整个编码序列以及内含子/外显子边界进行基因分型。测序分析揭示了PTEN不同区域的19种不同类型的突变（在外显子2、4、5、6、7以及内含子2和4的剪接位点以及3'UTR区域），包括3种沉默突变、8种错义突变、2种移码突变和6种剪接位点变异。在本研究观察到的变异中，已有报道在不同人群中存在三种错义突变，即319G>A（Asp106Asn）, 389G>A（Arg129Gln）和482G>A（Arg160Lys）。目前的结果表明，广泛的种系PTEN突变可能在乳腺癌的发病机制中起作用。
