2.5. Mutational Landscape
IRES lesions, TCGA
APC
In total, 34 metastatic specimens from 29 patients, prior to regorafenib treatment and passing quality control (histology, quality, and yield), were profiled to define the somatic mutational landscape of the cohort using whole exome sequencing (WES).It is largely recognized that CRC cells hold driver mutations in specific genes (i.e., APC, KRAS, BRAF, PIK3CA, and TP53). Therefore, we decided to investigate the mutation spectrum of these genes in our cohort. Using the TCGA database [Despite being known drivers in CRC, BRAF and PIK3CA mutation frequencies were lower than other genes shown in The relationship between mutated genes and PFS was evaluated; none were identified as significantly associated. This could be due to the small sample size of our cohort; however, we observed that KRAS mutations in amino acids 12 or 13 were identified in 5 out of 6 patients with IRES lesions, compared to 7 out of 17 in all other lesions. A mutation in amino acid 146 was only detected in ARES lesions in 2 out of 4 patients.To expand our analysis, we looked at the number of mutations affecting genes in the same well-described oncogenic pathways: TP53, MYC, Cell Cycle, TGF-β, PI3K, Hippo, WNT, NOTCH, and RTK-RAS. In our cohort, TGF-β is the pathway most affected by mutations (