HNSCC_CTNNA
Cell-cell adhesion genes CTNNA2 and CTNNA3 are novel tumor suppressors frequently mutated in head and neck carcinomas
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, representing a significant cause of morbidity and mortality. To explore the biological basis of HNSCC, we performed exome sequencing in four tumor-normal pairs. Among the 569 genes found to present somatic mutations, we selected 40 for further mutational analysis in 86 additional HNSCCs. Notably, we detected frequent mutations in the cell-cell adhesion genes CTNNA2 and CTNNA3 (8% in each of them). Functional studies revealed a remarkable increase in the migration and invasive ability of HNSCC cells after CTNNA2 and CTNNA3 silencing. In addition, HNSCC cells overexpressing mutated forms of each gene show increased migration and invasive ability compared to HNSCC cells overexpressing their wild-type counterparts. Analysis of the clinical relevance of these mutations demonstrated that they are associated with poor prognosis. Taken together, these findings suggest that CTNNA2 and CTNNA3 are novel tumor suppressor genes which are commonly mutated in HNSCC.