Imaging, Diagnosis, Prognosis Prognostic Role of PIK3CA Mutation in Colorectal Cancer: Cohort Study and Literature Review
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چکیده
Purpose:Mutations in PIK3CA [the gene encoding the p110a catalytic subunit of phosphatidylinositide3-kinase (PI3K)] play an important role in colorectal carcinogenesis. Experimental evidence suggests that PIK3CA exon 9 and exon 20mutations trigger different biologic effects, and that concomitant mutations in both exons 9 and 20 synergistically enhance tumorigenic effects. Thus, we hypothesized that PIK3CA exon 9 and exon 20 mutations might have differential effects on clinical outcome in colorectal cancer, and that concomitant PIK3CA exon 9 and 20 mutations might confer aggressive tumor behavior. Experimental Design: We sequenced PIK3CA by pyrosequencing in 1,170 rectal and colon cancers in two prospective cohort studies, and found 189 (16%) PIK3CAmutated tumors. Mortality HR according to PIK3CA status was computed using Cox proportional hazards model, adjusting for clinical and molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and BRAF and KRAS mutations. Results:Compared with PIK3CAwild-type cases, patients with concomitant PIK3CAmutations in exons 9 and 20 experienced significantly worse cancer-specific survival [log-rank P 1⁄4 0.031; multivariate HR 1⁄4 3.51; 95%confidence interval (CI): 1.28–9.62] andoverall survival (log-rank P1⁄40.0008;multivariateHR1⁄4 2.68; 95% CI: 1.24–5.77). PIK3CA mutation in either exon 9 or 20 alone was not significantly associated with patient survival. No significant interaction of PIK3CA mutation with BRAF or KRAS mutation was observed in survival analysis. Conclusion:Coexistence of PIK3CA (the PI3Kp110a subunit) exon 9 and 20mutations, but not PIK3CA mutation in either exon 9 or 20 alone, is associated with poor prognosis of colorectal cancer patients. Clin Cancer Res; 18(8); 2257–68. 2012 AACR.
منابع مشابه
Prognostic role of PIK3CA mutation in colorectal cancer: cohort study and literature review.
PURPOSE Mutations in PIK3CA [the gene encoding the p110α catalytic subunit of phosphatidylinositide-3-kinase (PI3K)] play an important role in colorectal carcinogenesis. Experimental evidence suggests that PIK3CA exon 9 and exon 20 mutations trigger different biologic effects, and that concomitant mutations in both exons 9 and 20 synergistically enhance tumorigenic effects. Thus, we hypothesize...
متن کاملPrognostic Role of PIK3CA Mutation in Colorectal Cancer: Cohort Study and Literature Review Running Title: PIK3CA Mutation in Colorectal Cancer
Funding: This work was supported by U.S. National Institute of Health [P01CA87969 (to S.E. Hankinson), P01CA55075 (to W.C. Willett), P50CA127003 (to C.S.F.), and R01CA151993 (to S.O.)]; the Bennett Family Fund for Targeted Therapies Research; and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. The content is solely the responsibility of the authors an...
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تاریخ انتشار 2012