Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population

Abstract

Activation of the phosphatidylinositol 3 0 -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 ¼ 0.0046) while PTEN loss was more frequent in microsatellite stable (MSS) CRC (P ¼ 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.

Prevalence ofPIK3CAmutations and the SNP rs17849079 in Arab breast cancer patients

“…Twentyfive CAF cells from 25 separate breast tumors were generated as The PIK3CA mutation status has been recently reported for colorectal and ovarian cancers in the Middle Eastern population 37,38 with frequencies of 12.4% and 3.9%, respectively. We present here the first report on the frequency and nature of PIK3CA mutations related to breast cancer in the Arab population.…”

The molecular background of mucinous carcinoma beyond MUC2

“…The PI3K pathway is normally inhibited by tumour suppressor gene PTEN. PIK3CA is more commonly mutated in MC (9-50%) than in NMC (7-12%) and a RR of 1.79 (95% CI 1.46-2.19) was found for MC in an analysis on mutational PIK3CA status [34, 58,59,[71][72][73][74]. Also, PIK3CA mutations occur more frequently in tumours that are localized in the proximal colon, as are MCs [3,4,34,73].…”

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of the Colon and Rectum

“…PIK3CA mutation and subsequent activation of the AKT pathway have been shown to play an important role in colorectal carcinogenesis and have been associated with KRAS mutation 12 and microsatellite instability. 13 PIK3CA mutation has further been associated with poor survival in resectable stage I to III colon cancer, with the adverse effect of PIK3CA mutation potentially limited to patients with KRAS wild-type tumors. 14 PIK3CA mutations have been associated with resistance to anti-EGFR therapy in several studies, 15,16 but not in others.…”