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Mutational analysis of driver genes defines the colorectal adenoma: in situ carcinoma transition
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SYSNO ASEP 0566473 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Mutational analysis of driver genes defines the colorectal adenoma: in situ carcinoma transition Author(s) Jungwirth, J. (CZ)
Urbanová, Markéta (UEM-P)
Boot, A. (NL)
Hošek, P. (CZ)
Bendová, Petra (UEM-P)
Šišková, Anna (UEM-P)
Švec, Jiří (UMG-J) RID
Kment, M. (CZ)
Tůmová, D. (CZ)
Summerá, S. (CZ)
Beneš, Z. (CZ)
Buchler, T. (CZ)
Kohout, P. (CZ)
Hucl, T. (CZ)
Matěj, R. (CZ)
Vodičková, Ludmila (UEM-P) RID
Wezel, T. (NL)
Vodička, Pavel (UEM-P) RID
Vymetálková, Veronika (UEM-P) RIDArticle number 2570 Source Title Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 12, č. 1 (2022)Number of pages 10 s. Language eng - English Country DE - Germany Keywords kras mutations ; braf ; classification ; cancer OECD category Genetics and heredity (medical genetics to be 3) R&D Projects NV18-03-00199 GA MZd - Ministry of Health (MZ) GA18-09709S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support UEM-P - RVO:68378041 ; UMG-J - RVO:68378050 UT WOS 000757107700016 EID SCOPUS 85124775184 DOI 10.1038/s41598-022-06498-9 Annotation A large proportion of colorectal carcinomas (CRC) evolve from colorectal adenomas. However, not all individuals with colonic adenomas have a risk of CRC substantially higher than those of the general population. The aim of the study was to determine the differences or similarities of mutation profile among low- and high-grade adenomas and in situ carcinoma with detailed follow up. We have investigated the mutation spectrum of well-known genes involved in CRC (such as APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, and TP53) in a large, well-defined series of 96 adenomas and in situ carcinomas using a high-throughput genotyping technique. Besides, the microsatellite instability and APC and MLH1 promoter methylation were studied as well. We observed a high frequency of pathogenic variants in the studied genes. The APC, KRAS and TP53 mutation frequencies were slightly lower in adenoma samples than in in situ carcinoma samples. Further, when we stratified mutation frequency based on the grade, the frequency distribution was as follows: low-grade adenoma-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%. The occurrence of KRAS mutation was associated with the presence of villous histology and methylation of the APC promoter was significantly associated with the presence of POLE genetic variations. However, no association was noticed with the presence of any singular mutation and occurrence of subsequent adenoma or CRC. Our data supports the multistep model of gradual accumulation of mutations, especially in the driver genes, such as APC, TP53 and KRAS. Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2023 Electronic address https://www.nature.com/articles/s41598-022-06498-9
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