The immune-related role of BRAF in melanoma

Sara Tomei, Davide Bedognetti, Valeria De Giorgi, Michele Sommariva, Sara Civini, Jennifer Reinboth, Muna J. Al-Hashmi, Maria Libera Ascierto, Qiuzhen Liu, Ben D. Ayotte, Andrea Worschech, Lorenzo Uccellini, Paolo A. Ascierto, David Stroncek, Giuseppe Palmieri, Lotfi Chouchane, Ena Wang, Francesco M. Marincola

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: The existence of a dichotomy between immunologically active and quiescent tumor 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. BRAF and NRAS mutations are commonly acquired during melanoma progression. Here we explored the role of BRAF and NRAS mutations in influencing the immune phenotype based on a classification previously identified by our group. Methods: One-hundred-thirteen melanoma metastases underwent microarray analysis and BRAF and NRAS genotyping. Allele-specific PCR was also performed in order 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 were able to distinguish the two immune-related phenotypes already described in melanoma, with the poor phenotype associated mostly with BRAF mutation. Noteworthy, such association was stronger in samples displaying low BRAF mRNA expression. However, when testing NRAS mutations, we were not able to find the same association. Conclusion: This study suggests that BRAF mutation-related specific transcripts associate with a poor phenotype in melanoma and provide a nest for further investigation.

Original languageEnglish
Pages (from-to)93-104
Number of pages12
JournalMolecular Oncology
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Jan 2015

Fingerprint

Melanoma
Phenotype
Mutation
Neoplasms
Mutation Rate
Microarray Analysis
Immunotherapy
Alleles
Neoplasm Metastasis
Polymerase Chain Reaction
Messenger RNA
Genes

Keywords

  • BRAF
  • Immune phenotype
  • Melanoma
  • NRAS

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cancer Research

Cite this

Tomei, S., Bedognetti, D., De Giorgi, V., Sommariva, M., Civini, S., Reinboth, J., ... Marincola, F. M. (2015). The immune-related role of BRAF in melanoma. Molecular Oncology, 9(1), 93-104. https://doi.org/10.1016/j.molonc.2014.07.014

The immune-related role of BRAF in melanoma. / Tomei, Sara; Bedognetti, Davide; De Giorgi, Valeria; Sommariva, Michele; Civini, Sara; Reinboth, Jennifer; Al-Hashmi, Muna J.; Ascierto, Maria Libera; Liu, Qiuzhen; Ayotte, Ben D.; Worschech, Andrea; Uccellini, Lorenzo; Ascierto, Paolo A.; Stroncek, David; Palmieri, Giuseppe; Chouchane, Lotfi; Wang, Ena; Marincola, Francesco M.

In: Molecular Oncology, Vol. 9, No. 1, 01.01.2015, p. 93-104.

Research output: Contribution to journalArticle

Tomei, S, Bedognetti, D, De Giorgi, V, Sommariva, M, Civini, S, Reinboth, J, Al-Hashmi, MJ, Ascierto, ML, Liu, Q, Ayotte, BD, Worschech, A, Uccellini, L, Ascierto, PA, Stroncek, D, Palmieri, G, Chouchane, L, Wang, E & Marincola, FM 2015, 'The immune-related role of BRAF in melanoma', Molecular Oncology, vol. 9, no. 1, pp. 93-104. https://doi.org/10.1016/j.molonc.2014.07.014
Tomei S, Bedognetti D, De Giorgi V, Sommariva M, Civini S, Reinboth J et al. The immune-related role of BRAF in melanoma. Molecular Oncology. 2015 Jan 1;9(1):93-104. https://doi.org/10.1016/j.molonc.2014.07.014
Tomei, Sara ; Bedognetti, Davide ; De Giorgi, Valeria ; Sommariva, Michele ; Civini, Sara ; Reinboth, Jennifer ; Al-Hashmi, Muna J. ; Ascierto, Maria Libera ; Liu, Qiuzhen ; Ayotte, Ben D. ; Worschech, Andrea ; Uccellini, Lorenzo ; Ascierto, Paolo A. ; Stroncek, David ; Palmieri, Giuseppe ; Chouchane, Lotfi ; Wang, Ena ; Marincola, Francesco M. / The immune-related role of BRAF in melanoma. In: Molecular Oncology. 2015 ; Vol. 9, No. 1. pp. 93-104.
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AU - Al-Hashmi, Muna J.

AU - Ascierto, Maria Libera

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AU - Uccellini, Lorenzo

AU - Ascierto, Paolo A.

AU - Stroncek, David

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