Interaction between p53 mutation and a somatic HDMX biomarker better defines metastatic potential in breast cancer

Anna M Grawenda; Elen K Møller; Suzanne Lam; Emmanouela Repapi; Amina F A S Teunisse; Grethe I G Alnæs; Anne-Lise Børresen-Dale; Vessela N Kristensen; Colin R Goding; Aart G Jochemsen; Hege Edvardsen; Gareth L Bond

doi:10.1158/0008-5472.CAN-14-2637

Interaction between p53 mutation and a somatic HDMX biomarker better defines metastatic potential in breast cancer

Anna M Grawenda, Elen K Møller, Suzanne Lam, Emmanouela Repapi, Amina F A S Teunisse, Grethe I G Alnæs, Anne-Lise Børresen-Dale, Vessela N Kristensen, Colin R Goding, Aart G Jochemsen, Hege Edvardsen, Gareth L Bond

Cancer and Genomic Sciences

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

11 Citations (Scopus)

Abstract

TP53 gene mutation is associated with poor prognosis in breast cancer, but additional biomarkers that can further refine the impact of the p53 pathway are needed to achieve clinical utility. In this study, we evaluated a role for the HDMX-S/FL ratio as one such biomarker, based on its association with other suppressor mutations that confer worse prognosis in sarcomas, another type of cancer that is surveilled by p53. We found that HDMX-S/FL ratio interacted with p53 mutational status to significantly improve prognostic capability in patients with breast cancer. This biomarker pair offered prognostic utility that was comparable with a microarray-based prognostic assay. Unexpectedly, the utility tracked independently of DNA-damaging treatments and instead with different tumor metastasis potential. Finally, we obtained evidence that this biomarker pair might identify patients who could benefit from anti-HDM2 strategies to impede metastatic progression. Taken together, our work offers a p53 pathway marker, which both refines our understanding of the impact of p53 activity on prognosis and harbors potential utility as a clinical tool.

Original language	English
Pages (from-to)	698-708
Number of pages	11
Journal	Cancer Research
Volume	75
Issue number	4
Early online date	3 Feb 2015
DOIs	https://doi.org/10.1158/0008-5472.CAN-14-2637
Publication status	Published - 15 Feb 2015

Keywords

Biomarkers, Tumor/biosynthesis
Breast Neoplasms/drug therapy
Cell Cycle Proteins
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
Humans
Lymphatic Metastasis/genetics
Mutation
Neoplasm Staging
Nuclear Proteins/biosynthesis
Proto-Oncogene Proteins/biosynthesis
Tumor Suppressor Protein p53/biosynthesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Grawenda, A. M., Møller, E. K., Lam, S., Repapi, E., Teunisse, A. F. A. S., Alnæs, G. I. G., Børresen-Dale, A-L., Kristensen, V. N., Goding, C. R., Jochemsen, A. G., Edvardsen, H., & Bond, G. L. (2015). Interaction between p53 mutation and a somatic HDMX biomarker better defines metastatic potential in breast cancer. Cancer Research, 75(4), 698-708. Advance online publication. https://doi.org/10.1158/0008-5472.CAN-14-2637

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title = "Interaction between p53 mutation and a somatic HDMX biomarker better defines metastatic potential in breast cancer",

abstract = "TP53 gene mutation is associated with poor prognosis in breast cancer, but additional biomarkers that can further refine the impact of the p53 pathway are needed to achieve clinical utility. In this study, we evaluated a role for the HDMX-S/FL ratio as one such biomarker, based on its association with other suppressor mutations that confer worse prognosis in sarcomas, another type of cancer that is surveilled by p53. We found that HDMX-S/FL ratio interacted with p53 mutational status to significantly improve prognostic capability in patients with breast cancer. This biomarker pair offered prognostic utility that was comparable with a microarray-based prognostic assay. Unexpectedly, the utility tracked independently of DNA-damaging treatments and instead with different tumor metastasis potential. Finally, we obtained evidence that this biomarker pair might identify patients who could benefit from anti-HDM2 strategies to impede metastatic progression. Taken together, our work offers a p53 pathway marker, which both refines our understanding of the impact of p53 activity on prognosis and harbors potential utility as a clinical tool.",

keywords = "Biomarkers, Tumor/biosynthesis, Breast Neoplasms/drug therapy, Cell Cycle Proteins, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Humans, Lymphatic Metastasis/genetics, Mutation, Neoplasm Staging, Nuclear Proteins/biosynthesis, Proto-Oncogene Proteins/biosynthesis, Tumor Suppressor Protein p53/biosynthesis",

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doi = "10.1158/0008-5472.CAN-14-2637",

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Grawenda, AM, Møller, EK, Lam, S, Repapi, E, Teunisse, AFAS, Alnæs, GIG, Børresen-Dale, A-L, Kristensen, VN, Goding, CR, Jochemsen, AG, Edvardsen, H & Bond, GL 2015, 'Interaction between p53 mutation and a somatic HDMX biomarker better defines metastatic potential in breast cancer', Cancer Research, vol. 75, no. 4, pp. 698-708. https://doi.org/10.1158/0008-5472.CAN-14-2637

TY - JOUR

T1 - Interaction between p53 mutation and a somatic HDMX biomarker better defines metastatic potential in breast cancer

AU - Grawenda, Anna M

AU - Møller, Elen K

AU - Lam, Suzanne

AU - Repapi, Emmanouela

AU - Teunisse, Amina F A S

AU - Alnæs, Grethe I G

AU - Børresen-Dale, Anne-Lise

AU - Kristensen, Vessela N

AU - Goding, Colin R

AU - Jochemsen, Aart G

AU - Edvardsen, Hege

AU - Bond, Gareth L

PY - 2015/2/15

Y1 - 2015/2/15

N2 - TP53 gene mutation is associated with poor prognosis in breast cancer, but additional biomarkers that can further refine the impact of the p53 pathway are needed to achieve clinical utility. In this study, we evaluated a role for the HDMX-S/FL ratio as one such biomarker, based on its association with other suppressor mutations that confer worse prognosis in sarcomas, another type of cancer that is surveilled by p53. We found that HDMX-S/FL ratio interacted with p53 mutational status to significantly improve prognostic capability in patients with breast cancer. This biomarker pair offered prognostic utility that was comparable with a microarray-based prognostic assay. Unexpectedly, the utility tracked independently of DNA-damaging treatments and instead with different tumor metastasis potential. Finally, we obtained evidence that this biomarker pair might identify patients who could benefit from anti-HDM2 strategies to impede metastatic progression. Taken together, our work offers a p53 pathway marker, which both refines our understanding of the impact of p53 activity on prognosis and harbors potential utility as a clinical tool.

AB - TP53 gene mutation is associated with poor prognosis in breast cancer, but additional biomarkers that can further refine the impact of the p53 pathway are needed to achieve clinical utility. In this study, we evaluated a role for the HDMX-S/FL ratio as one such biomarker, based on its association with other suppressor mutations that confer worse prognosis in sarcomas, another type of cancer that is surveilled by p53. We found that HDMX-S/FL ratio interacted with p53 mutational status to significantly improve prognostic capability in patients with breast cancer. This biomarker pair offered prognostic utility that was comparable with a microarray-based prognostic assay. Unexpectedly, the utility tracked independently of DNA-damaging treatments and instead with different tumor metastasis potential. Finally, we obtained evidence that this biomarker pair might identify patients who could benefit from anti-HDM2 strategies to impede metastatic progression. Taken together, our work offers a p53 pathway marker, which both refines our understanding of the impact of p53 activity on prognosis and harbors potential utility as a clinical tool.

KW - Biomarkers, Tumor/biosynthesis

KW - Breast Neoplasms/drug therapy

KW - Cell Cycle Proteins

KW - Disease-Free Survival

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Lymphatic Metastasis/genetics

KW - Mutation

KW - Neoplasm Staging

KW - Nuclear Proteins/biosynthesis

KW - Proto-Oncogene Proteins/biosynthesis

KW - Tumor Suppressor Protein p53/biosynthesis

U2 - 10.1158/0008-5472.CAN-14-2637

DO - 10.1158/0008-5472.CAN-14-2637

M3 - Article

C2 - 25649770

SN - 0008-5472

VL - 75

SP - 698

EP - 708

JO - Cancer Research

JF - Cancer Research

IS - 4

ER -

Interaction between p53 mutation and a somatic HDMX biomarker better defines metastatic potential in breast cancer

Abstract

Keywords

UN SDGs

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