Mutational analysis of driver genes defines the colorectal adenoma: in situ carcinoma transition
To dissect the genetics in the evolvement of colorectal adenomas into colorectal carcinomas (CRC) we have analyzed the mutation spectrum of genes involved in CRC (APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, TP53) in 96 adenomas and in situ carcinomas by a high-throughput genotyping technique. We found a high frequency of pathogenic variants in these genes. The APC, KRAS and TP53 mutation frequencies were lower in adenomas than in in situ carcinoma samples. The frequency distribution of mutations was as follows: low-grade adenomas-high-grade adenomas-in situ carcinoma: APC gene 42.9-56.0-54.5%; KRAS gene 32.7-32.0-45.5%; TP53 gene 8.2-20.0-18.2%. KRAS mutations occurred mainly in villous histology, APC promoter methylation associated with POLE genetic variations. There is a multistep model of gradual accumulation of mutations in the driver genes.
Jungwirth, J., Urbanová, M., Boot, A., Hošek, P., Bendová, P., Šišková, A., Švec, J., Kment, M., Tůmová, D., Summerová, S., Beneš, Z., Buchler, T., Kohout, P., Hucl, T., Matěj, R., Vodičková, L., van Wezel, T., Vodička, P., Vymetálková, V.: (2022) Mutational analysis of driver genes defines the colorectal adenoma: in situ carcinoma transition. Scientific Reports. 12(1): 2570. doi: 10.1038/s41598-022-06498-9.