Mutational analysis of driver genes defines the colorectal adenoma: in situ carcinoma transition

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F22%3A00566473" target="_blank" >RIV/68378041:_____/22:00566473 - isvavai.cz</a>

Alternative codes found

RIV/00023001:_____/22:00082398 RIV/00216208:11140/22:10440234 RIV/68378050:_____/22:00566473 RIV/00064173:_____/22:43923011 and 3 more

Result on the web

<a href="https://www.nature.com/articles/s41598-022-06498-9" target="_blank" >https://www.nature.com/articles/s41598-022-06498-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-022-06498-9" target="_blank" >10.1038/s41598-022-06498-9</a>

Result language

angličtina

Original language name

Mutational analysis of driver genes defines the colorectal adenoma: in situ carcinoma transition

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10603 - Genetics and heredity (medical genetics to be 3)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Volume of the periodical

12

Issue of the periodical within the volume

1

Country of publishing house

DE - GERMANY

Number of pages

10

Pages from-to

2570

UT code for WoS article

000757107700016

EID of the result in the Scopus database

2-s2.0-85124775184