Oncogenic mutations in gastric cancer with microsatellite instability.

作者: Giovanni Corso , Sérgia Velho , Joana Paredes , Corrado Pedrazzani , Diana Martins

DOI: 10.1016/J.EJCA.2010.09.008

关键词:

摘要: Abstract Aim Mitogen-activated protein kinase ( MAPK ) cascade and phosphatidylinositol 3-kinase PI3K survival pathways are frequently activated in the progression of gastrointestinal malignancies. In this study, we aimed to determine frequency gene mutations members these – Epithelial Growth Factor Receptor EGFR , KRAS, BRAF, PIK3CA MLK3 a series 63 gastric carcinomas with high levels microsatellite instability (MSI). Methods Gene mutation analysis was performed by PCR amplification followed direct sequencing. selected tumour cases, expression evaluated immunohistochemistry. Association studies between molecular data clinicopathologic characteristics were performed. Results Mutations (3′-untranslated region [UTR] polyA repeat), KRAS genes occurred 30 (47.6%), 11 (17.5%), 9 (14.3%) 2 (3.2%) MSI cancer (GC) respectively. No BRAF or hotspot identified. Overall, at least one found 55.6% (35/63) carcinomas. From those mutant cases 40.0% (14/35) them had concomitant mutations, always involving deletions. Interestingly, observed significant associations oncogenic female gender p =0.046) old age diagnosis =0.001) intestinal subtype =0.043). Conclusion Our results show that carcinoma shows activation - pathways. Within all alterations found, deletions A13 repeats common, suggesting event as an important biomarker for stratification GC patients treatment inhibitors.

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