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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 LU ; Ekedahl, Henrik LU ; Lauss, Martin LU ; Harbst, Katja LU ; Carneiro, Ana LU ; Enoksson, Jens LU ; Rosengren, Frida LU ; Werner Hartman, Linda LU ; Törngren, Therese LU and Kvist, Anders LU , et al. (2015) In Oncotarget 6(14). p.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,... (More)
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. (Less)
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Oncotarget
volume
6
issue
14
pages
12297 - 12309
publisher
Impact Journals, LLC
external identifiers
  • pmid:25909218
  • wos:000359008200041
  • scopus:84931405791
ISSN
1949-2553
DOI
10.18632/oncotarget.3655
language
English
LU publication?
yes
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0f854506-59fb-481c-8334-edd374ba1e62 (old id 5340743)
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http://www.ncbi.nlm.nih.gov/pubmed/25909218?dopt=Abstract
date added to LUP
2015-05-02 11:56:14
date last changed
2017-09-24 04:08:14
@article{0f854506-59fb-481c-8334-edd374ba1e62,
  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.},
  author       = {Cirenajwis, Helena and Ekedahl, Henrik and Lauss, Martin and Harbst, Katja and Carneiro, Ana and Enoksson, Jens and Rosengren, Frida and Werner Hartman, Linda and Törngren, Therese and Kvist, Anders and Fredlund, Erik and Bendahl, Pär-Ola and Jirström, Karin and Lundgren, Lotta and Howlin, Jillian and Borg, Åke and Gruvberger, Sofia and Saal, Lao and Nielsen, Kari and Ringnér, Markus and Tsao, Hensin and Olsson, Håkan and Ingvar, Christian and Staaf, Johan and Jönsson, Göran B},
  issn         = {1949-2553},
  language     = {eng},
  number       = {14},
  pages        = {12297--12309},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.},
  url          = {http://dx.doi.org/10.18632/oncotarget.3655},
  volume       = {6},
  year         = {2015},
}