Whole-exome sequencing detection of the somatic mutations associated with the tumorigenesis and gefitinib-response of mucoepidermoid carcinomas

Abstract Background: We performed whole-exome sequencing (WES) on the sputum and blood samples of a MEC patient exploring the genetic alternations underlying the mechanism of mucoepidermoid carcinomas (MEC) and gefitinib response.Methods: We previously reported a 10-year old MEC patient who was cured after a complete response to gefitinib treatment. Whole-exome sequencing (WES) was performed on the samples of this patient to detect somatic mutations. Detected genes harboring somatic mutations were compared with previously reported mutant genes related to MEC.Results: Somatic mutations were detected in 13 previously reported oncogene and tumor suppressors, and enriched in apoptosis (RIPK1, SPTA1, and ACTG1). The loss and gain of phosphorylation amino acids occurred in 8 of the 34 non-synonymous mutations, which resided in ARL6, DNAH11, PGM5, PRAMEF15, RALGAPB, RANBP2, TTN, and UBN1. TTN bared two Ala to Thr mutations. Among the 50 genes containing detected somatic mutations, ADAM28, DYSF, GP2, PPP2R5B, and TTN were also detected in a previous study; and all of these overlaps were identified in low and intermediate grade samples.Conclusions: These findings underline the possibility of the accumulated somatic mutations in the tumor suppressor genes and oncogenes might contribute to the tumorigenesis of our MEC patient, which have potential applications for the therapies of MEC.