TY  - JOUR
AU  - Ahadova, Aysel
AU  - Stenzinger, A.
AU  - Seppälä, T.
AU  - Hüneburg, R.
AU  - Kloor, Matthias
AU  - Bläker, H.
TI  - The two-in-one hit model of the short-cut carcinogenesis of colorectal carcinomas in MLH1-associated Lynch syndrome. [Das Two-in-one-hit-Modell der beschleunigten Genese von kolorektalen Karzinomen beim MLH1-assoziierten Lynch-Syndrom].
JO  - Die Pathologie
VL  - 44
IS  - Supp. 3
SN  - 2731-7188
CY  - [Berlin]
PB  - Springer Medizin Verlag GmbH
M1  - DKFZ-2023-02290
SP  - 188-192
PY  - 2023
N1  - #EA:F210#LA:F210# / 2023 Dec;44(Suppl 3):188-192
AB  - In a recently published study a new genetic hypothesis was established that explained the existence of CTNNB1 mutations in Lynch syndrome-associated colorectal carcinomas (MLH1-LS-CRC). This hypothesis states that a mitotic recombination on chromosome 3p simultaneously leads to inactivation of the mismatch repair gene MLH1 and to the activation of CTNNB1. This explains the increased frequency of CTNNB1 mutations in MLH1-LS-CRC compared with other colon carcinomas. To test this hypothesis, various experiments were carried out that show that the first phase of recombination occurs in non-cancerous tissues, which favours the development of CTNNB1 mutations. This mechanism could explain the rapid tumour progression in MLH1-LS-CRC. The results highlight the importance of mitotic recombination in carcinogenesis and provide an insight into the genetic basis of colorectal carcinoma in the context of Lynch syndrome.
KW  - Adenoma (Other)
KW  - DNA mismatch repair (Other)
KW  - Genetic recombination (Other)
KW  - Human CTNNB1 protein (Other)
KW  - Tumor supressor genes (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37932477
DO  - DOI:10.1007/s00292-023-01245-x
UR  - https://inrepo02.dkfz.de/record/285255
ER  -