PMS2 expression decrease causes severe problems in mismatch repair

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Kasela , M , Nyström , M & Kansikas , M 2019 , ' PMS2 expression decrease causes severe problems in mismatch repair ' , Human Mutation , vol. 40 , no. 7 , pp. 904-907 . https://doi.org/10.1002/humu.23756

Title: PMS2 expression decrease causes severe problems in mismatch repair
Author: Kasela, Mariann; Nyström, Minna; Kansikas, Minttu
Contributor: University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Genetics
University of Helsinki, Molecular and Integrative Biosciences Research Programme
Date: 2019-07
Language: eng
Number of pages: 4
Belongs to series: Human Mutation
ISSN: 1059-7794
URI: http://hdl.handle.net/10138/304378
Abstract: PMS2 is one of the four susceptibility genes in Lynch syndrome (LS), the most common cancer syndrome in the world. Inherited mutations in DNA mismatch repair (MMR) genes, MLH1, MSH2, and MSH6, account for approximately 90% of LS, while a relatively small number of LS families segregate a PMS2 mutation. This and the low cancer penetrance in PMS2 families suggest that PMS2 is only a moderate or low-risk susceptibility gene. We have previously shown that even a partial expression decrease in MLH1, MSH2, or MSH6 suggests that heterozygous LS mutation carriers have MMR malfunction in constitutive tissues. Whether and how PMS2 expression decrease affects the repair capability is not known. Here, we show that PMS2 knockdown cells retaining 19%, 33%, or 53% of PMS2 expression all have significantly reduced MMR efficiency. Surprisingly, the cells retaining expression levels comparable to PMS2 mutation carriers indicate the lowest repair efficiency.
Subject: colorectal cancer
Lynch syndrome
mismatch repair
mRNA expression
PMS2
1184 Genetics, developmental biology, physiology
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