PMS2 expression decrease causes severe problems in mismatch repair

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

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. This article is protected by copyright. All rights reserved.
Alkuperäiskielienglanti
LehtiHuman Mutation
ISSN1059-7794
DOI - pysyväislinkit
TilaJulkaistu - 4 huhtikuuta 2019
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 1184 Genetiikka, kehitysbiologia, fysiologia

Lainaa tätä

@article{1cf845255d704ba39af0eed9d110fefc,
title = "PMS2 expression decrease causes severe problems in mismatch repair",
abstract = "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. This article is protected by copyright. All rights reserved.",
keywords = "colorectal cancer, Lynch syndrome, mismatch repair, mRNA expression, PMS2, 1184 Genetics, developmental biology, physiology",
author = "Mariann Kasela and Minna Nystr{\"o}m and Minttu Kansikas",
year = "2019",
month = "4",
day = "4",
doi = "10.1002/humu.23756",
language = "English",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "John Wiley & Sons, Ltd",

}

PMS2 expression decrease causes severe problems in mismatch repair. / Kasela, Mariann; Nyström, Minna; Kansikas, Minttu.

julkaisussa: Human Mutation, 04.04.2019.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - PMS2 expression decrease causes severe problems in mismatch repair

AU - Kasela, Mariann

AU - Nyström, Minna

AU - Kansikas, Minttu

PY - 2019/4/4

Y1 - 2019/4/4

N2 - 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. This article is protected by copyright. All rights reserved.

AB - 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. This article is protected by copyright. All rights reserved.

KW - colorectal cancer

KW - Lynch syndrome

KW - mismatch repair

KW - mRNA expression

KW - PMS2

KW - 1184 Genetics, developmental biology, physiology

U2 - 10.1002/humu.23756

DO - 10.1002/humu.23756

M3 - Article

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

ER -