Understanding melanoma progression by gene expression signatures

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5 Citations (Scopus)

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.

Original languageEnglish
Title of host publicationCancer Genomics
Subtitle of host publicationMolecular Classification, Prognosis and Response Prediction
PublisherSpringer Netherlands
Pages47-78
Number of pages32
Volume9789400758421
ISBN (Electronic)9789400758421
ISBN (Print)9400758413, 9789400758414
DOIs
Publication statusPublished - Sep 1 2013

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Tímár, J., Barbai, T., Gyorffy, B., & Rásó, E. (2013). Understanding melanoma progression by gene expression signatures. In Cancer Genomics: Molecular Classification, Prognosis and Response Prediction (Vol. 9789400758421, pp. 47-78). Springer Netherlands. https://doi.org/10.1007/978-94-007-5842-1_2