Mutational landscapes of tongue carcinoma reveal recurrent mutations in genes of therapeutic and prognostic relevance

• DOI: 10.1186/s13073-015-0219-2
• Publication Date: 2015-09-22T23:28:23Z
• Authors: Andre Luiz Vettore; Kalpana Ramnarayanan; Gregory Poore; Kevin Lim; Choon Kiat Ong; Kie Kyon Huang; Hui Sun Leong; Fui Teen Chong; Tony Kiat-Hon Lim; Weng Khong Lim; Ioana Cutcutache; John R. Mcpherson; Yuka Suzuki; Shenli Zhang; Thakshayeni Skant...; Weining Wang; Daniel SW Tan; Byoung Chul Cho; Bin Tean Teh; Steve Rozen; Patrick Tan; N. Gopalakrishna ...
• Keywords: Human genetics; Relevance

Carcinoma of the oral tongue (OTSCC) is most common malignancy cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in OTSCC epidemiological profile, with increasing incidence younger patients, females never-smokers. Here, we sought to characterize genomic landscape determine factors that may delineate genetic basis this disease, inform prognosis identify targets for therapeutic intervention. Seventy-eight cases were subjected whole-exome (n = 18) targeted deep sequencing 60). While mutation was TP53, differed from previously described cohorts patients head neck tumors: OTSCCs demonstrated mutations DST RNF213, while alterations CDKN2A NOTCH1 significantly less frequent. Despite lack reported mutations, integrated analysis showed enrichments affecting Notch signaling OTSCC. Importantly, these pathway prognostic on multivariate analyses. A high proportion also presented drug targetable chromatin remodeling genes. Patients harboring actionable pathways more likely succumb recurrent disease compared those who did not, suggesting former should be considered treatment compounds future trials. Our study defines Asian mutational landscape, highlighting key role tumorigenesis. We observed somatic multiple therapeutically relevant genes, which represent candidate highly lethal tumor type.