Molecular stratification of metastatic melanoma using gene expression profiling : Prediction of survival outcome and benefit from molecular targeted therapy
| Autor: | Sofia K. Gruvberger-Saal, Katja Harbst, Christian Ingvar, Linda Werner-Hartman, Anders Kvist, Kari Nielsen, Erik Fredlund, Henrik Ekedahl, Frida Rosengren, Åke Borg, Helena Cirenajwis, Håkan Olsson, Lao H. Saal, Hensin Tsao, Ana Carneiro, Martin Lauss, Göran Jönsson, Lotta Lundgren, Jillian Howlin, Markus Ringnér, Johan Staaf, Karin Jirström, Pär-Ola Bendahl, Jens Enoksson, Therese Törngren |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Oncology
BRAF inhibitor Male medicine.medical_specialty Skin Neoplasms medicine.medical_treatment Population DNA Mutational Analysis Antineoplastic Agents Kaplan-Meier Estimate Biology Bioinformatics Cancer Vaccines Targeted therapy BRAF Cohort Studies 03 medical and health sciences 0302 clinical medicine Internal medicine medicine melanoma Humans Molecular Targeted Therapy education 030304 developmental biology Aged Proportional Hazards Models 0303 health sciences education.field_of_study Proportional hazards model Melanoma Gene Expression Profiling Middle Aged medicine.disease Prognosis Phenotype Vaccine therapy 3. Good health Gene expression profiling Cancer and Oncology 030220 oncology & carcinogenesis Cutaneous melanoma gene expression Female mutation Transcriptome Research Paper |
| Zdroj: | Oncotarget ResearcherID Oncotarget; 6(14), pp 12297-12309 (2015) |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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