A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants

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A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants. / Drost, Mark; Zonneveld, José B M; van Hees, Sandrine; Rasmussen, Lene Juel; Hofstra, Robert M W; de Wind, Niels.

In: Human Mutation, Vol. 33, No. 3, 2012, p. 488-94.

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

Harvard

Drost, M, Zonneveld, JBM, van Hees, S, Rasmussen, LJ, Hofstra, RMW & de Wind, N 2012, 'A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants', Human Mutation, vol. 33, no. 3, pp. 488-94. https://doi.org/10.1002/humu.22000

APA

Drost, M., Zonneveld, J. B. M., van Hees, S., Rasmussen, L. J., Hofstra, R. M. W., & de Wind, N. (2012). A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants. Human Mutation, 33(3), 488-94. https://doi.org/10.1002/humu.22000

Vancouver

Drost M, Zonneveld JBM, van Hees S, Rasmussen LJ, Hofstra RMW, de Wind N. A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants. Human Mutation. 2012;33(3):488-94. https://doi.org/10.1002/humu.22000

Author

Drost, Mark ; Zonneveld, José B M ; van Hees, Sandrine ; Rasmussen, Lene Juel ; Hofstra, Robert M W ; de Wind, Niels. / A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants. In: Human Mutation. 2012 ; Vol. 33, No. 3. pp. 488-94.

Bibtex

@article{0fe5fe9a19964a85a008942dc1377900,
title = "A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants",
abstract = "Lynch syndrome (LS) is an autosomal dominant disorder that predisposes to colon, endometrial, and other cancers. LS is caused by a heterozygous germline mutation in one of the DNA mismatch repair (MMR) genes. A significant proportion of all mutations found in suspected LS patients comprises single amino acid alterations. The pathogenicity of these variants of uncertain significance (VUS) is difficult to assess, precluding diagnosis of carriers and their relatives. Here we present a rapid cell-free assay to investigate MMR activity of MSH2 or MSH6 VUS. We used this assay to analyze a series of MSH2 and MSH6 VUS, selected from the Leiden Open Variation Database. Whereas a significant fraction of the MSH2 VUS has lost MMR activity, suggesting pathogenicity, the large majority of the MSH6 VUS appears MMR proficient. We anticipate that this assay will be an important tool in the development of a comprehensive and widely applicable diagnostic procedure for LS-associated VUS.",
keywords = "Biological Assay, Blotting, Western, Colorectal Neoplasms, Hereditary Nonpolyposis, DNA-Binding Proteins, Humans, MutS Homolog 2 Protein, Mutation, Missense, Polymerase Chain Reaction",
author = "Mark Drost and Zonneveld, {Jos{\'e} B M} and {van Hees}, Sandrine and Rasmussen, {Lene Juel} and Hofstra, {Robert M W} and {de Wind}, Niels",
note = "{\textcopyright} 2011 Wiley Periodicals, Inc.",
year = "2012",
doi = "10.1002/humu.22000",
language = "English",
volume = "33",
pages = "488--94",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "JohnWiley & Sons, Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants

AU - Drost, Mark

AU - Zonneveld, José B M

AU - van Hees, Sandrine

AU - Rasmussen, Lene Juel

AU - Hofstra, Robert M W

AU - de Wind, Niels

N1 - © 2011 Wiley Periodicals, Inc.

PY - 2012

Y1 - 2012

N2 - Lynch syndrome (LS) is an autosomal dominant disorder that predisposes to colon, endometrial, and other cancers. LS is caused by a heterozygous germline mutation in one of the DNA mismatch repair (MMR) genes. A significant proportion of all mutations found in suspected LS patients comprises single amino acid alterations. The pathogenicity of these variants of uncertain significance (VUS) is difficult to assess, precluding diagnosis of carriers and their relatives. Here we present a rapid cell-free assay to investigate MMR activity of MSH2 or MSH6 VUS. We used this assay to analyze a series of MSH2 and MSH6 VUS, selected from the Leiden Open Variation Database. Whereas a significant fraction of the MSH2 VUS has lost MMR activity, suggesting pathogenicity, the large majority of the MSH6 VUS appears MMR proficient. We anticipate that this assay will be an important tool in the development of a comprehensive and widely applicable diagnostic procedure for LS-associated VUS.

AB - Lynch syndrome (LS) is an autosomal dominant disorder that predisposes to colon, endometrial, and other cancers. LS is caused by a heterozygous germline mutation in one of the DNA mismatch repair (MMR) genes. A significant proportion of all mutations found in suspected LS patients comprises single amino acid alterations. The pathogenicity of these variants of uncertain significance (VUS) is difficult to assess, precluding diagnosis of carriers and their relatives. Here we present a rapid cell-free assay to investigate MMR activity of MSH2 or MSH6 VUS. We used this assay to analyze a series of MSH2 and MSH6 VUS, selected from the Leiden Open Variation Database. Whereas a significant fraction of the MSH2 VUS has lost MMR activity, suggesting pathogenicity, the large majority of the MSH6 VUS appears MMR proficient. We anticipate that this assay will be an important tool in the development of a comprehensive and widely applicable diagnostic procedure for LS-associated VUS.

KW - Biological Assay

KW - Blotting, Western

KW - Colorectal Neoplasms, Hereditary Nonpolyposis

KW - DNA-Binding Proteins

KW - Humans

KW - MutS Homolog 2 Protein

KW - Mutation, Missense

KW - Polymerase Chain Reaction

U2 - 10.1002/humu.22000

DO - 10.1002/humu.22000

M3 - Journal article

C2 - 22102614

VL - 33

SP - 488

EP - 494

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 3

ER -

ID: 38418760