| Autor: |
Michele Sommariva, Francesco M. Marincola, Lotfi Chouchane, Maria Libera Ascierto, Muna Al Hashmi, Giuseppe Palmieri, Davide Bedognetti, Valeria De Giorgi, Paolo A. Ascierto, Ena Wang, Sara Tomei, David F. Stroncek |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
Qatar Foundation Annual Research Conference Proceedings Volume 2014 Issue 1. |
| Popis: |
BACKGROUND. The existence of a dichotomy between immunologically active and quiescent phenotypes has been recently recognized in several types of cancer. The activation of a Th1 type of immune signature has been shown to confer better prognosis and likelihood to respond to immunotherapy. However, whether such dichotomy depends on the genetic make-up of individual cancers is not known yet. In melanoma, BRAF and NRAS mutations are frequently acquired during development. We recently proposed a genetic classification of melanoma metastases based on copy number variation and consistency of genes expressed in vivo and in vitro. We found that genes consistently expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) were critical for oncogenesis and their respective copy number influenced their expression. Most importantly, these genes were able to categorize melanoma metastases into two divergent phenotypes (TARA class: transcriptional adjustments related to amplification/deletions): one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A) and the other one with prevalent expression of genes associated with melanoma signaling and with a Th1 immune phenotype (Class B). An intermediate third class (Class C) was further identified. Here, we tested whether these phenotypes might be at least in part explained by BRAF and NRAS mutations in melanoma. METHODS. One-hundred-thirteen melanoma metastases were processed for microarray analysis and BRAF and NRAS sequencing. Allele-specific PCR (AS-PCR) was also performed to exclude low-frequency mutations. RESULTS. Comparison between BRAF and NRAS mutant versus wild type samples identified mostly constituents or regulators of MAPK and related pathways. When testing gene lists discriminative of BRAF, NRAS and MAPK alterations, we found that 112 BRAF-specific transcripts (p |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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