Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • Grawenda, Anna M1
  • Møller, Elen K2
  • Lam, Suzanne3
  • Repapi, Emmanouela1
  • Teunisse, Amina F A S3
  • Alnæs, Grethe I G4
  • Børresen-Dale, Anne-Lise2
  • Kristensen, Vessela N5
  • Goding, Colin R1
  • Jochemsen, Aart G3
  • Edvardsen, Hege4
  • Bond, Gareth L6
  • 1 Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Oxford, United Kingdom. , (United Kingdom)
  • 2 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway. KG Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. , (Norway)
  • 3 Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands. , (Netherlands)
  • 4 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway. , (Norway)
  • 5 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway. KG Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Department of Clinical Molecular Biology (EpiGen), Medical Division, Akershus University Hospital, Lørenskog, Norway. , (Norway)
  • 6 Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Oxford, United Kingdom. [email protected] , (United Kingdom)
Type
Published Article
Journal
Cancer Research
Publisher
American Association for Cancer Research
Publication Date
Feb 15, 2015
Volume
75
Issue
4
Pages
698–708
Identifiers
DOI: 10.1158/0008-5472.CAN-14-2637
PMID: 25649770
Source
Medline
License
Unknown

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.

Report this publication

Statistics

Seen <100 times