Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients. / Andersen, Sofie Dabros; Liberti, Sascha Emilie; Lützen, Anne; Drost, Mark; Bernstein, Inge; Nilbert, Mef; Dominguez, Mev; Nyström, Minna; Hansen, Thomas Van Overeem; Christoffersen, Janus Wiese; Jäger, Anne Charlotte; de Wind, Niels; Nielsen, Finn Cilius; Tørring, Pernille M; Rasmussen, Lene Juel.

In: Human Mutation, Vol. 33, No. 12, 12.2012, p. 1647-1655.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Andersen, SD, Liberti, SE, Lützen, A, Drost, M, Bernstein, I, Nilbert, M, Dominguez, M, Nyström, M, Hansen, TVO, Christoffersen, JW, Jäger, AC, de Wind, N, Nielsen, FC, Tørring, PM & Rasmussen, LJ 2012, 'Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients', Human Mutation, vol. 33, no. 12, pp. 1647-1655. https://doi.org/10.1002/humu.22153

APA

Andersen, S. D., Liberti, S. E., Lützen, A., Drost, M., Bernstein, I., Nilbert, M., Dominguez, M., Nyström, M., Hansen, T. V. O., Christoffersen, J. W., Jäger, A. C., de Wind, N., Nielsen, F. C., Tørring, P. M., & Rasmussen, L. J. (2012). Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients. Human Mutation, 33(12), 1647-1655. https://doi.org/10.1002/humu.22153

Vancouver

Andersen SD, Liberti SE, Lützen A, Drost M, Bernstein I, Nilbert M et al. Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients. Human Mutation. 2012 Dec;33(12):1647-1655. https://doi.org/10.1002/humu.22153

Author

Andersen, Sofie Dabros ; Liberti, Sascha Emilie ; Lützen, Anne ; Drost, Mark ; Bernstein, Inge ; Nilbert, Mef ; Dominguez, Mev ; Nyström, Minna ; Hansen, Thomas Van Overeem ; Christoffersen, Janus Wiese ; Jäger, Anne Charlotte ; de Wind, Niels ; Nielsen, Finn Cilius ; Tørring, Pernille M ; Rasmussen, Lene Juel. / Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients. In: Human Mutation. 2012 ; Vol. 33, No. 12. pp. 1647-1655.

Bibtex

@article{32f887a9f61a4cbcaceef36f8132a6b5,
title = "Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients",
abstract = "Germline mutations in the human DNA mismatch repair (MMR) genes MSH2 and MLH1 are associated with the inherited cancer disorder Lynch Syndrome (LS), also known as Hereditary Nonpolyposis Colorectal Cancer or HNPCC. A proportion of MSH2 and MLH1 mutations found in suspected LS patients give rise to single amino acid substitutions. The functional consequences in regards to pathogenicity of many of these variants are unclear. We have examined the functionality of a panel of MLH1 missense mutations found in LS families, by testing the variant proteins in functional assays, addressing subcellular localization and protein-protein interaction with the dimer partner PMS2 and the MMR-associated exonuclease 1. We show that a significant proportion of examined variant proteins have functional defects in either subcellular localization or protein-protein interactions, which is suspected to lead to the cancer phenotype observed in patients. Moreover, the obtained results correlate well with reported MMR activity and with in silico analysis for a majority of the variants.",
author = "Andersen, {Sofie Dabros} and Liberti, {Sascha Emilie} and Anne L{\"u}tzen and Mark Drost and Inge Bernstein and Mef Nilbert and Mev Dominguez and Minna Nystr{\"o}m and Hansen, {Thomas Van Overeem} and Christoffersen, {Janus Wiese} and J{\"a}ger, {Anne Charlotte} and {de Wind}, Niels and Nielsen, {Finn Cilius} and T{\o}rring, {Pernille M} and Rasmussen, {Lene Juel}",
note = "{\textcopyright} 2012 Wiley Periodicals, Inc.",
year = "2012",
month = dec,
doi = "10.1002/humu.22153",
language = "English",
volume = "33",
pages = "1647--1655",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "JohnWiley & Sons, Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients

AU - Andersen, Sofie Dabros

AU - Liberti, Sascha Emilie

AU - Lützen, Anne

AU - Drost, Mark

AU - Bernstein, Inge

AU - Nilbert, Mef

AU - Dominguez, Mev

AU - Nyström, Minna

AU - Hansen, Thomas Van Overeem

AU - Christoffersen, Janus Wiese

AU - Jäger, Anne Charlotte

AU - de Wind, Niels

AU - Nielsen, Finn Cilius

AU - Tørring, Pernille M

AU - Rasmussen, Lene Juel

N1 - © 2012 Wiley Periodicals, Inc.

PY - 2012/12

Y1 - 2012/12

N2 - Germline mutations in the human DNA mismatch repair (MMR) genes MSH2 and MLH1 are associated with the inherited cancer disorder Lynch Syndrome (LS), also known as Hereditary Nonpolyposis Colorectal Cancer or HNPCC. A proportion of MSH2 and MLH1 mutations found in suspected LS patients give rise to single amino acid substitutions. The functional consequences in regards to pathogenicity of many of these variants are unclear. We have examined the functionality of a panel of MLH1 missense mutations found in LS families, by testing the variant proteins in functional assays, addressing subcellular localization and protein-protein interaction with the dimer partner PMS2 and the MMR-associated exonuclease 1. We show that a significant proportion of examined variant proteins have functional defects in either subcellular localization or protein-protein interactions, which is suspected to lead to the cancer phenotype observed in patients. Moreover, the obtained results correlate well with reported MMR activity and with in silico analysis for a majority of the variants.

AB - Germline mutations in the human DNA mismatch repair (MMR) genes MSH2 and MLH1 are associated with the inherited cancer disorder Lynch Syndrome (LS), also known as Hereditary Nonpolyposis Colorectal Cancer or HNPCC. A proportion of MSH2 and MLH1 mutations found in suspected LS patients give rise to single amino acid substitutions. The functional consequences in regards to pathogenicity of many of these variants are unclear. We have examined the functionality of a panel of MLH1 missense mutations found in LS families, by testing the variant proteins in functional assays, addressing subcellular localization and protein-protein interaction with the dimer partner PMS2 and the MMR-associated exonuclease 1. We show that a significant proportion of examined variant proteins have functional defects in either subcellular localization or protein-protein interactions, which is suspected to lead to the cancer phenotype observed in patients. Moreover, the obtained results correlate well with reported MMR activity and with in silico analysis for a majority of the variants.

U2 - 10.1002/humu.22153

DO - 10.1002/humu.22153

M3 - Journal article

C2 - 22753075

VL - 33

SP - 1647

EP - 1655

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 12

ER -

ID: 38418635