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

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

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dc.contributor.author Cirenajwis, Helena en_US
dc.contributor.author Ekedahl, Henrik en_US
dc.contributor.author Lauss, Martin en_US
dc.contributor.author Harbst, Katja en_US
dc.contributor.author Carneiro, Ana en_US
dc.contributor.author Enoksson, Jens en_US
dc.contributor.author Rosengren, Frida en_US
dc.contributor.author Werner-Hartman, Linda en_US
dc.contributor.author Törngren, Therese en_US
dc.contributor.author Kvist, Anders en_US
dc.contributor.author Fredlund, Erik en_US
dc.contributor.author Bendahl, Pär-Ola en_US
dc.contributor.author Jirström, Karin en_US
dc.contributor.author Lundgren, Lotta en_US
dc.contributor.author Howlin, Jillian en_US
dc.contributor.author Borg, Åke en_US
dc.contributor.author Gruvberger-Saal, Sofia K. en_US
dc.contributor.author Saal, Lao H. en_US
dc.contributor.author Nielsen, Kari en_US
dc.contributor.author Ringnér, Markus en_US
dc.contributor.author Tsao, Hensin en_US
dc.contributor.author Olsson, Håkan en_US
dc.contributor.author Ingvar, Christian en_US
dc.contributor.author Staaf, Johan en_US
dc.contributor.author Jönsson, Göran en_US
dc.date.accessioned 2015-08-03T14:02:29Z
dc.date.issued 2015 en_US
dc.identifier.citation 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. en
dc.identifier.issn 1949-2553 en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820895
dc.description.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. en
dc.language.iso en_US en
dc.publisher Impact Journals LLC en
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494939/pdf/ en
dash.license LAA en_US
dc.subject gene expression en
dc.subject melanoma en
dc.subject BRAF en
dc.subject BRAF inhibitor en
dc.subject mutation en
dc.title Molecular stratification of metastatic melanoma using gene expression profiling : Prediction of survival outcome and benefit from molecular targeted therapy en
dc.type Journal Article en_US
dc.description.version Version of Record en
dc.relation.journal Oncotarget en
dash.depositing.author Tsao, Hensin en_US
dc.date.available 2015-08-03T14:02:29Z

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