Oncogenic mutations in colorectal cancer, indications for anatomical sites, and targeted intervention

Oncogenic mutations, such as KRAS, in colorectal cancer patients are considered standard molecular biomarkers that predict the clinical benefit for the targeted intervention with EGFR inhibitors. In addition, these mutations are associated with specific anatomical area in the colon tumor development, as BRAF mutations with the microsatellite instability. Methods: In this translational study we aim to assess the mutation frequencies of the EGFR [hotspot area and polyadenine deletions (A13_del)], KRAS, BRAFV600E, and PIK3CA oncogenes in a series of 280 colorectal cancer patients. Microsatellite instability phenotype is considered in this series. All patients' clinicopathological data were considered for statistical analysis and associations. Results: In this study, we verified multiple associations between oncogenic mutations and specified clinicopathological tumor features. Respectively, we identified the following significant results: 1) EGFR A13_deletions are associated with right colon carcinoma (22.2% vs. 3.3%; p<0.005), mucinous histotype (16% vs. 7.8%; p=0.042), G3 grading (19% vs. 7.3%; p=0.024) and microsatellite instability status (p<0.005); 2) PIK3CA mutations are related mucinous histotype (12% vs. 4.4%; p=0.021) 3) KRASG12 and KRASG13mutations are correlated respectively with the left (91.4% vs. 59.3%) and right (40.7% vs. 8.6%) colon cancer development (p<0.005), and finally 4) microsatellite instability is associated with right colon tumors (28.4% vs. 5.5%; p<0.005). Conclusions: Mostly, we verified a high frequency rate of the KRASG13 and EGFR A13_del oncogene mutations in right colon cancer; whereas KRASG12 codon mutation occurs more frequently in left colon cancers. In particular, we assessed that right colon cancer is associated with specific molecular characteristics, in comparison to left colon tumors. These evidences, in association with specific clinicopathological data, can delineate novel approaches for the colorectal cancer classification and targeted intervention.