The next generation of metastatic melanoma

Uncovering the genetic variants for anti-BRAF therapy response

Rosamaria Pinto, Simona De Summa, Sabino Strippoli, Brunella Pilato, Amalia Azzariti, Gabriella Guida, Michele Guida, Stefania Tommasi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Metastatic melanoma (MM) is a highly aggressive cancer with a median overall survival of 6-9 months, notwithstanding the numerous efforts in development of new therapeutic approaches. To this aim we tested the clinical applicability of the Ion Torrent Personal Genome Machine to simultaneously screen MM patients in order to individuate new or already known SNPs and mutations able to predict the duration of response to BRAF inhibitors. An Ampliseq Custom Panel, including 11 crucial full length genes involved in melanoma carcinogenesis and therapy response pathways, was created and used to analyze 25 MM patients. We reported BRAFV600 and NRASQ61 mutations in 68% and 24% of samples, respectively. Moreover, we more frequently identified the following alterations related to BRAF status: PIK3CAI391M (44%) and KITD737N (36%) mutations, CTLA4T17A (52%), MC1RV60L (32%) and MITFS473A (60%) polymorphisms. Considering the progression free survival (PFS), statistical analyses showed that BRAFV600 patients without any of these more frequent alterations had a higher median PFS. Protein structure changes seem to be due to these variants by in silico analysis. In conclusion, a Next-Generation Sequencing approach with custom panel may provide new information to evaluate tumor-specific therapeutic susceptibility and individual prognosis to improve the care of MM patients.

Original languageEnglish
Pages (from-to)25135-25149
Number of pages15
JournalOncotarget
Volume7
Issue number18
DOIs
Publication statusPublished - May 1 2016

Fingerprint

Melanoma
Mutation
Disease-Free Survival
Therapeutics
Survival Analysis
Computer Simulation
Single Nucleotide Polymorphism
Neoplasms
Carcinogenesis
Genome
Ions
Survival
Genes
Proteins

Keywords

  • BRAF inhibitors
  • Ion Torrent
  • Metastatic melanoma
  • Next generation sequencing
  • Progression

ASJC Scopus subject areas

  • Oncology

Cite this

The next generation of metastatic melanoma : Uncovering the genetic variants for anti-BRAF therapy response. / Pinto, Rosamaria; De Summa, Simona; Strippoli, Sabino; Pilato, Brunella; Azzariti, Amalia; Guida, Gabriella; Guida, Michele; Tommasi, Stefania.

In: Oncotarget, Vol. 7, No. 18, 01.05.2016, p. 25135-25149.

Research output: Contribution to journalArticle

Pinto R, De Summa S, Strippoli S, Pilato B, Azzariti A, Guida G et al. The next generation of metastatic melanoma: Uncovering the genetic variants for anti-BRAF therapy response. Oncotarget. 2016 May 1;7(18):25135-25149. https://doi.org/10.18632/oncotarget.7175
Pinto, Rosamaria ; De Summa, Simona ; Strippoli, Sabino ; Pilato, Brunella ; Azzariti, Amalia ; Guida, Gabriella ; Guida, Michele ; Tommasi, Stefania. / The next generation of metastatic melanoma : Uncovering the genetic variants for anti-BRAF therapy response. In: Oncotarget. 2016 ; Vol. 7, No. 18. pp. 25135-25149.
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