Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population
Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population
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DOI：
10.1038/sj.onc.1211013
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发表时间：
2008-06-05
期刊：
影响因子：
8
通讯作者：
Al-Kuraya, K. S.
中科院分区：
文献类型：
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作者：
Abubaker, J.;Bavi, P.;Al-Kuraya, K. S.
磷脂酰肌醇3 '-激酶（PI 3 K）/AKT途径的激活导致细胞增殖和存活的增加。PI 3 K催化亚基PIK 3CA内的体细胞突变是增加PI 3 K活性的常见原因，并且被认为在许多癌症类型中是致癌的。很少有报道涉及PIK 3CA突变与肿瘤进展之间的关联，特别是在微卫星不稳定（MSI）结直肠癌（CRC）中。在本研究中，我们评估了一系列410个中东CRC和13个结肠细胞系中的PIK 3CA突变状态，以研究MSI病例中PIK 3CA突变的患病率、CRC中的PTEN表达以及这组患者治疗靶向的可能性。PIK 3CA突变在四个测试的细胞系和51个结直肠癌中发现（12.2%）。这四个突变的细胞系中有三个是MSI。66.1%的大肠癌组织中PTEN失活。此外，我们观察到PIK 3CA突变和MSI状态之间的强关联（P = 0.0046），而PTEN丢失在微卫星稳定（MSS）CRC中更常见（P = 0.043）。在沙特CRC队列中PI 3 K/AKT通路的遗传改变的高患病率、MSI亚组中PIK 3CA突变的优势及其可能参与该CRC亚组的发展/进展是我们研究的一些重要发现。
Activation of the phosphatidylinositol 3'-kinase (PI3K)/AKT pathway results in an increase in cell proliferation and survival. Somatic mutations within the PI3K catalytic subunit, PIK3CA are common cause of increasing PI3K activity and are believed to be oncogenic in many cancer types. Few reports addressed the association between PIK3CA mutations and tumor progression specifically in microsatellite instable (MSI) colorectal cancer (CRC). In the present study, we have evaluated PIK3CA mutational status in a series of 410 Middle Eastern CRC and 13 colon cell lines to study the prevalence of PIK3CA mutations in MSI cases, PTEN expression in CRC and possibility of therapeutic targeting of this set of patients. PIK3CA mutations were found in four of the cell lines tested and 51 colorectal carcinomas (12.2%). Three of these four mutated cell lines were MSI. PTEN was inactivated in 66.1% of the CRC. Furthermore, we observed a strong association between PIK3CA mutations and MSI status (P = 0.0046) while PTEN loss was more frequent in microsatellite stable (MSS) CRC (P = 0.043). A high prevalence of genetic alterations in PI3K/AKT pathway in Saudi cohort of CRC, predominance of PIK3CA mutations in the MSI subgroup and their possible involvement in development/progression of this subset of CRC are some of the significant findings of our study.