Poor prognosis of constitutive γ-H2AX expressing triple-negative breast cancers is associated with telomere length

Anika Nagelkerke; Simon J A van Kuijk; John W. M. Martens; Fred C G J Sweep; Nicoline Hoogerbrugge; Johan Bussink; Paul N Span

doi:10.2217/bmm.15.2

Poor prognosis of constitutive γ-H2AX expressing triple-negative breast cancers is associated with telomere length

Anika Nagelkerke, Simon J A van Kuijk, John W. M. Martens, Fred C G J Sweep, Nicoline Hoogerbrugge, Johan Bussink, Paul N Span^*

^*Corresponding author for this work

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

14 Citations (Scopus)

Abstract

AIM: Here, we set out to establish whether endogenous γ-H2AX is a biomarker in triple-negative breast cancer.

METHODS: We explored the association of γ-H2AX with mutation status and sensitivity to 139 different anticancer drugs in up to 41 breast cancer cell lines. Further, we correlated γ-H2AX expression in breast cancer tumor tissues with telomere length.

RESULTS: γ-H2AX positive breast cancer cells exhibit more mutations, and - when p53 mutated - have shorter telomeres. In breast cancer patients γ-H2AX is also related to shorter telomeres, which was in turn associated with poorer prognosis of triple-negative breast cancer patients.

CONCLUSION: Thus, endogenous γ-H2AX is associated with short telomeres, which might offer a specific target for therapy for triple-negative breast cancer patients.

Original language	English
Pages (from-to)	383-90
Number of pages	8
Journal	Biomarkers in medicine
Volume	9
Issue number	4
DOIs	https://doi.org/10.2217/bmm.15.2
Publication status	Published - 2015
Externally published	Yes

Keywords

BRCA1 Protein/genetics
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Histones/metabolism
Humans
Mutation
Prognosis
Telomere/genetics
Triple Negative Breast Neoplasms/diagnosis

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Cite this

@article{88c8898a365c4a0dac6bf3822866bc14,

title = "Poor prognosis of constitutive γ-H2AX expressing triple-negative breast cancers is associated with telomere length",

abstract = "AIM: Here, we set out to establish whether endogenous γ-H2AX is a biomarker in triple-negative breast cancer.METHODS: We explored the association of γ-H2AX with mutation status and sensitivity to 139 different anticancer drugs in up to 41 breast cancer cell lines. Further, we correlated γ-H2AX expression in breast cancer tumor tissues with telomere length.RESULTS: γ-H2AX positive breast cancer cells exhibit more mutations, and - when p53 mutated - have shorter telomeres. In breast cancer patients γ-H2AX is also related to shorter telomeres, which was in turn associated with poorer prognosis of triple-negative breast cancer patients.CONCLUSION: Thus, endogenous γ-H2AX is associated with short telomeres, which might offer a specific target for therapy for triple-negative breast cancer patients.",

keywords = "BRCA1 Protein/genetics, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Histones/metabolism, Humans, Mutation, Prognosis, Telomere/genetics, Triple Negative Breast Neoplasms/diagnosis",

author = "Anika Nagelkerke and {van Kuijk}, {Simon J A} and Martens, {John W. M.} and Sweep, {Fred C G J} and Nicoline Hoogerbrugge and Johan Bussink and Span, {Paul N}",

year = "2015",

doi = "10.2217/bmm.15.2",

language = "English",

volume = "9",

pages = "383--90",

journal = "Biomarkers in medicine",

issn = "1752-0363",

publisher = "FUTURE MEDICINE LTD",

number = "4",

}

TY - JOUR

T1 - Poor prognosis of constitutive γ-H2AX expressing triple-negative breast cancers is associated with telomere length

AU - Nagelkerke, Anika

AU - van Kuijk, Simon J A

AU - Martens, John W. M.

AU - Sweep, Fred C G J

AU - Hoogerbrugge, Nicoline

AU - Bussink, Johan

AU - Span, Paul N

PY - 2015

Y1 - 2015

N2 - AIM: Here, we set out to establish whether endogenous γ-H2AX is a biomarker in triple-negative breast cancer.METHODS: We explored the association of γ-H2AX with mutation status and sensitivity to 139 different anticancer drugs in up to 41 breast cancer cell lines. Further, we correlated γ-H2AX expression in breast cancer tumor tissues with telomere length.RESULTS: γ-H2AX positive breast cancer cells exhibit more mutations, and - when p53 mutated - have shorter telomeres. In breast cancer patients γ-H2AX is also related to shorter telomeres, which was in turn associated with poorer prognosis of triple-negative breast cancer patients.CONCLUSION: Thus, endogenous γ-H2AX is associated with short telomeres, which might offer a specific target for therapy for triple-negative breast cancer patients.

AB - AIM: Here, we set out to establish whether endogenous γ-H2AX is a biomarker in triple-negative breast cancer.METHODS: We explored the association of γ-H2AX with mutation status and sensitivity to 139 different anticancer drugs in up to 41 breast cancer cell lines. Further, we correlated γ-H2AX expression in breast cancer tumor tissues with telomere length.RESULTS: γ-H2AX positive breast cancer cells exhibit more mutations, and - when p53 mutated - have shorter telomeres. In breast cancer patients γ-H2AX is also related to shorter telomeres, which was in turn associated with poorer prognosis of triple-negative breast cancer patients.CONCLUSION: Thus, endogenous γ-H2AX is associated with short telomeres, which might offer a specific target for therapy for triple-negative breast cancer patients.

KW - BRCA1 Protein/genetics

KW - Cell Line, Tumor

KW - Gene Expression Regulation, Neoplastic

KW - Histones/metabolism

KW - Humans

KW - Mutation

KW - Prognosis

KW - Telomere/genetics

KW - Triple Negative Breast Neoplasms/diagnosis

U2 - 10.2217/bmm.15.2

DO - 10.2217/bmm.15.2

M3 - Article

C2 - 25808442

SN - 1752-0363

VL - 9

SP - 383

EP - 390

JO - Biomarkers in medicine

JF - Biomarkers in medicine

IS - 4

ER -