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Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.

Author:
  • Helena Cirenajwis
  • Henrik Ekedahl
  • Martin Lauss
  • Katja Harbst
  • Ana Carneiro
  • Jens Enoksson
  • Frida Rosengren
  • Linda Werner Hartman
  • Therese Törngren
  • Anders Kvist
  • Erik Fredlund
  • Pär-Ola Bendahl
  • Karin Jirström
  • Lotta Lundgren
  • Jillian Howlin
  • Åke Borg
  • Sofia Gruvberger
  • Lao Saal
  • Kari Nielsen
  • Markus Ringnér
  • Hensin Tsao
  • Håkan Olsson
  • Christian Ingvar
  • Johan Staaf
  • Göran B Jönsson
Publishing year: 2015
Language: English
Pages: 12297-12309
Publication/Series: Oncotarget
Volume: 6
Issue: 14
Document type: Journal article
Publisher: Impact Journals, LLC

Abstract english

Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.

Keywords

  • Cancer and Oncology

Other

Published
  • Melanoma Genomics
  • ISSN: 1949-2553
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90