TY - JOUR
T1 - The next generation of metastatic melanoma
T2 - Uncovering the genetic variants for anti-BRAF therapy response
AU - Pinto, Rosamaria
AU - De Summa, Simona
AU - Strippoli, Sabino
AU - Pilato, Brunella
AU - Azzariti, Amalia
AU - Guida, Gabriella
AU - Guida, Michele
AU - Tommasi, Stefania
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - BRAF inhibitors
KW - Ion Torrent
KW - Metastatic melanoma
KW - Next generation sequencing
KW - Progression
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U2 - 10.18632/oncotarget.7175
DO - 10.18632/oncotarget.7175
M3 - Article
AN - SCOPUS:84967262963
VL - 7
SP - 25135
EP - 25149
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 18
ER -