Research Papers:

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 and Stefania Tommasi

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Oncotarget. 2016; 7:25135-25149. https://doi.org/10.18632/oncotarget.7175

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Rosamaria Pinto1, Simona De Summa1, Sabino Strippoli2, Brunella Pilato1, Amalia Azzariti3, Gabriella Guida4, Michele Guida2, Stefania Tommasi1

1IRCCS Istituto Tumori “Giovanni Paolo II”, Molecular Genetics Laboratory, Bari, Italy

2IRCCS Istituto Tumori “Giovanni Paolo II”, Oncology Unit, Bari, Italy

3IRCCS Istituto Tumori “Giovanni Paolo II”, Clinical and Preclinical Pharmacology Laboratory, Bari, Italy

4University of Bari, Department of Medical Biochemistry, Bari, Italy

Correspondence to:

Stefania Tommasi, email: [email protected]

Keywords: metastatic melanoma, next generation sequencing, BRAF inhibitors, progression, Ion Torrent

Received: October 19, 2015     Accepted: January 24, 2016     Published: February 03, 2016


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.

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