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Understanding Melanoma Progression by Gene Expression Signatures

  • J. Tímár
  • T. Barbai
  • B. Győrffy
  • E. Rásó
Chapter

Abstract

Malignant melanoma is the most aggressive cancer in humans and understanding this unique biological behavior may help to design better prognosticators and more efficient therapies. However, malignant melanoma is a heterogenous tumor etiologically (UV-induced or not), morphologically and genetically driven by various oncogens (B-RAF, N-RAS, KIT) and suppressor genes (CDKN2A, p53, PTEN). There are a significant number of studies in which prognostic gene and protein signatures were defined based on either analysis of the primary tumors (metastasis initiating gene set) or melanoma metastases (metastasis maintenance gene set) affecting progression of the disease or survival of the patient. These studies provided prognostic signatures of minimal overlap. Here we demonstrate consensus prognostic gene and protein sets derived from primary and metastatic tumor tissues. It is of note that although there were rare overlaps concerning the composing individual genes in these sets, network analysis defined the common pathways driving melanoma progression: cell proliferation, apoptosis, motility, and immune mechanisms. Malignant melanoma is chemoresistant, the genetic background of which has been unknown for a long time, but new genomic analyses have identified complex genetic alterations responsible for this phenotype involving DNA repair genes and oncogene signaling pathways. The advent of immunotherapy of melanoma placed the previously defined immune signature-associated genomic prognosticators into a new perspective, suggesting that it might also be a powerful predictor. Target therapy of malignant melanoma has changed the standard therapy based on IFN and dacarbazine. Target therapy of B-RAF and KIT mutated melanomas is based on careful selection of tumors with activating/sensitizing mutations, but has immediately raised the issue of genetic basis of constitutive or acquired resistances.

Keywords

Melanoma Cell Human Melanoma Uveal Melanoma Vasculogenic Mimicry Skin Melanoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgement

This work was supported by grants ETT and TAMOP 4.2.1B.-09/1/KMR-2010-0001.

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • J. Tímár
    • 1
    • 2
  • T. Barbai
    • 1
  • B. Győrffy
    • 1
  • E. Rásó
    • 1
    • 2
  1. 1.2nd Department of PathologySemmelweis UniversityBudapestHungary
  2. 2.Tumor Progression Research GroupNational Academy of Sciences-Semmelweis UniversityBudapestHungary

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