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

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.

SUBMITTER: Cirenajwis H

PROVIDER: S-EPMC4494939 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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

Cirenajwis Helena H Ekedahl Henrik H Lauss Martin M Harbst Katja K Carneiro Ana A Enoksson Jens J Rosengren Frida F Werner-Hartman Linda L Törngren Therese T Kvist Anders A Fredlund Erik E Bendahl Pär-Ola PO Jirström Karin K Lundgren Lotta L Howlin Jillian J Borg Åke Å Gruvberger-Saal Sofia K SK Saal Lao H LH Nielsen Kari K Ringnér Markus M Tsao Hensin H Olsson Håkan H Ingvar Christian C Staaf Johan J Jönsson Göran G

Oncotarget 20150501 14

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 ...[more]

PMID: 25909218

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Dataset Information

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

Publications

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

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