The breast cancer susceptibility allele CHEK2*1100delC promotes genomic instability in a knock-in mouse model

El Mustapha Bahassi; C. Gail Penner; Susan B. Robbins; Elisia Tichy; Estrella Feliciano; Moying Yin; Li Liang; Li Deng; Jay A. Tischfield; Peter J. Stambrook

doi:10.1016/j.mrfmmm.2006.11.025

The breast cancer susceptibility allele CHEK2*1100delC promotes genomic instability in a knock-in mouse model

El Mustapha Bahassi, C. Gail Penner, Susan B. Robbins, Elisia Tichy, Estrella Feliciano, Moying Yin, Li Liang, Li Deng, Jay A. Tischfield, Peter J. Stambrook

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Allelic variants of CHEK2 contribute to an elevated risk for human breast cancer and possibly other cancer types. In particular, the CHEK2*1100delC polymorphic variant has been identified as a low-penetrance breast cancer susceptibility allele in breast cancer families with wild type BRCA1 and BRCA2. To better understand the molecular basis by which this allele increases risk for disease, we have generated a mouse in which the wild type CHEK2 (Chk2 in mouse) allele has been replaced with the 1100delC variant. Mouse embryo fibroblasts (MEFs) derived from these mice have an altered cell cycle profile in which a far greater proportion of cells are in S-phase and in G2 (4N) compared with wild type cells. The mutant cells show signs of spontaneous genomic instability as indicated by polyploidy and an increase in DNA double strand breaks.

Original language	English (US)
Pages (from-to)	201-209
Number of pages	9
Journal	Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume	616
Issue number	1-2
DOIs	https://doi.org/10.1016/j.mrfmmm.2006.11.025
State	Published - Mar 1 2007

All Science Journal Classification (ASJC) codes

Molecular Biology
Genetics
Health, Toxicology and Mutagenesis

Keywords

Breast cancer
CHEK2
DNA damage
Genomic instability
Mouse model

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10.1016/j.mrfmmm.2006.11.025

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Bahassi, E. M., Penner, C. G., Robbins, S. B., Tichy, E., Feliciano, E., Yin, M., Liang, L., Deng, L., Tischfield, J. A., & Stambrook, P. J. (2007). The breast cancer susceptibility allele CHEK2*1100delC promotes genomic instability in a knock-in mouse model. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 616(1-2), 201-209. https://doi.org/10.1016/j.mrfmmm.2006.11.025

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title = "The breast cancer susceptibility allele CHEK2*1100delC promotes genomic instability in a knock-in mouse model",

abstract = "Allelic variants of CHEK2 contribute to an elevated risk for human breast cancer and possibly other cancer types. In particular, the CHEK2*1100delC polymorphic variant has been identified as a low-penetrance breast cancer susceptibility allele in breast cancer families with wild type BRCA1 and BRCA2. To better understand the molecular basis by which this allele increases risk for disease, we have generated a mouse in which the wild type CHEK2 (Chk2 in mouse) allele has been replaced with the 1100delC variant. Mouse embryo fibroblasts (MEFs) derived from these mice have an altered cell cycle profile in which a far greater proportion of cells are in S-phase and in G2 (4N) compared with wild type cells. The mutant cells show signs of spontaneous genomic instability as indicated by polyploidy and an increase in DNA double strand breaks.",

keywords = "Breast cancer, CHEK2, DNA damage, Genomic instability, Mouse model",

author = "Bahassi, {El Mustapha} and Penner, {C. Gail} and Robbins, {Susan B.} and Elisia Tichy and Estrella Feliciano and Moying Yin and Li Liang and Li Deng and Tischfield, {Jay A.} and Stambrook, {Peter J.}",

note = "Funding Information: This work was supported in part by NIH grants U02 Es011038, CA 90934 and P39-ES06096. ET was supported by training grant ES07250. We gratefully thank Sandy Schwemberger and George Babcock for their guidance and help with the flow cytometry.",

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doi = "10.1016/j.mrfmmm.2006.11.025",

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Bahassi, EM, Penner, CG, Robbins, SB, Tichy, E, Feliciano, E, Yin, M, Liang, L, Deng, L, Tischfield, JA & Stambrook, PJ 2007, 'The breast cancer susceptibility allele CHEK2*1100delC promotes genomic instability in a knock-in mouse model', Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, vol. 616, no. 1-2, pp. 201-209. https://doi.org/10.1016/j.mrfmmm.2006.11.025

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AU - Bahassi, El Mustapha

AU - Penner, C. Gail

AU - Robbins, Susan B.

AU - Tichy, Elisia

AU - Feliciano, Estrella

AU - Yin, Moying

AU - Liang, Li

AU - Deng, Li

AU - Tischfield, Jay A.

AU - Stambrook, Peter J.

N1 - Funding Information: This work was supported in part by NIH grants U02 Es011038, CA 90934 and P39-ES06096. ET was supported by training grant ES07250. We gratefully thank Sandy Schwemberger and George Babcock for their guidance and help with the flow cytometry.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - Allelic variants of CHEK2 contribute to an elevated risk for human breast cancer and possibly other cancer types. In particular, the CHEK2*1100delC polymorphic variant has been identified as a low-penetrance breast cancer susceptibility allele in breast cancer families with wild type BRCA1 and BRCA2. To better understand the molecular basis by which this allele increases risk for disease, we have generated a mouse in which the wild type CHEK2 (Chk2 in mouse) allele has been replaced with the 1100delC variant. Mouse embryo fibroblasts (MEFs) derived from these mice have an altered cell cycle profile in which a far greater proportion of cells are in S-phase and in G2 (4N) compared with wild type cells. The mutant cells show signs of spontaneous genomic instability as indicated by polyploidy and an increase in DNA double strand breaks.

AB - Allelic variants of CHEK2 contribute to an elevated risk for human breast cancer and possibly other cancer types. In particular, the CHEK2*1100delC polymorphic variant has been identified as a low-penetrance breast cancer susceptibility allele in breast cancer families with wild type BRCA1 and BRCA2. To better understand the molecular basis by which this allele increases risk for disease, we have generated a mouse in which the wild type CHEK2 (Chk2 in mouse) allele has been replaced with the 1100delC variant. Mouse embryo fibroblasts (MEFs) derived from these mice have an altered cell cycle profile in which a far greater proportion of cells are in S-phase and in G2 (4N) compared with wild type cells. The mutant cells show signs of spontaneous genomic instability as indicated by polyploidy and an increase in DNA double strand breaks.

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The breast cancer susceptibility allele CHEK2*1100delC promotes genomic instability in a knock-in mouse model

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