We found that gene mutations/deletions are frequent in mesothelioma and occur through a variety of DNA alterations. We identified genes implicated in malignant mesothelioma: SETD2, SMARCC1, PBRM1. Previous next-generation studies (NGS) underestimated the frequency of genetic alterations in malignant mesothelioma because NGS mainly identifies nucleotide level mutations. Our findings are of general relevance to the field of cancer research that relies almost exclusively on NGS to identify gene alterations in cancer biopsies, and uses this information to design specific molecular therapies. An integrated approach that includes a high-density comparative genomic hybridization array and NGS or targeted-NGS, as conducted here, may reveal additional genes that are inactivated by mechanisms other than point mutations. This information may inform us on how to design more effective molecular therapies.
Yoshie Yoshikawa, Mitsuru Emi, Tomoko Hashimoto-Tamaoki*, Masaki Ohmuraya, Ayuko Sato, Tohru Tsujimura, Seiki Hasegawa, Takashi Nakano, AND Masaki Nasu, Sandra Pastorino, Agata Szymiczek, Angela Bononi, Mika Tanji, Ian Pagano, Giovanni Gaudino, Andrea Napolitano, Chandra Goparaju, Harvey I Pass, Haining Yang, Michele Carbone
November 11, 2016 | doi: 10.1001/jamaoncol.2016.5487