Mutations in colorectal cancer progression from granular and non-granular laterally spreading tumors. Homo sapiens

We previously analyzed epigenetic aberrations in colorectal laterallyspreading tumors (LSTs) and found that intermediate-methylation LSTswere significantly associated with KRAS-mutation and were mostlygranular type LST (LST-G) and low-methylation LSTs were significantlyassociated with absence of KRAS/BRAF mutation and were mostlynon-granular LST (LST-NG). In this study, we conducted targeted exonsequencing study including 38 candidate driver genes to gain insightinto how these genes modulate the genesis and progression of LST. Therewas no significant difference in the frequency of total mutationsbetween LST-G and LST-NG. Genes associated with RTK/RAS signalingpathway were mutated more frequently in LST-G than LST-NG, especially/KRAS/ mutation. Both LSTs showed high frequency of /APC/ mutation evenat adenoma stage, suggesting its involvement in initiation stage of LST,like adenoma-carcinoma sequence. /TP53/mutation was never detected byadenoma stage, but specifically detected in early cancer samplesin bothLST-G and LST-NG, suggesting its involvement in cancer development fromadenoma. /TP53/ mutation occurred during development of intramucosalcancer in LST-NG, but during development of cancer with submucosalinvasion in LST-G, suggesting involvement of /TP53/ mutation at earlierstage in LST-NG.