Molecular stratification of metastatic melanoma using gene expression profiling : Prediction of survival outcome and benefit from molecular targeted therapy
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Author
Cirenajwis, Helena
Ekedahl, Henrik
Lauss, Martin
Harbst, Katja
Carneiro, Ana
Enoksson, Jens
Rosengren, Frida
Werner-Hartman, Linda
Törngren, Therese
Kvist, Anders
Fredlund, Erik
Bendahl, Pär-Ola
Jirström, Karin
Lundgren, Lotta
Howlin, Jillian
Borg, Åke
Gruvberger-Saal, Sofia K.
Saal, Lao H.
Nielsen, Kari
Ringnér, Markus
Olsson, Håkan
Ingvar, Christian
Staaf, Johan
Jönsson, Göran
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Cirenajwis, H., H. Ekedahl, M. Lauss, K. Harbst, A. Carneiro, J. Enoksson, F. Rosengren, et al. 2015. “Molecular stratification of metastatic melanoma using gene expression profiling : Prediction of survival outcome and benefit from molecular targeted therapy.” Oncotarget 6 (14): 12297-12309.Abstract
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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494939/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820895
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