2012 YI Awards Abstracts.indd

Head and neck squamous cell carcinoma (HNSCC) encompasses malignancies that arise in the mucosa of the upper aerodigestive tract. Recent high throughput DNA sequencing revealed HNSCC mutation profiles including genes that control several cancer cell characteristics, including dysregulation of proliferation and death signals, induction of inflammatory responses, and reprogramming of cell metabolism. Emerging evidence suggests an evolutionarily conserved family, the pyrin-containing NLR (nucleotide binding domain, leucine-rich repeats containing) proteins, play fundamental roles in modulating the aforementioned processes, however, their functions in carcinogenesis still remain elusive. This study aims to assess the clinicopathologic and genetic characteristics associated with novel NLRP genes mutations identified in HNSCC by whole exome sequence analysis. The mutation landscape of 74 HNSCC patients treated at the University of Pittsburgh Medical Center was revealed using whole exome sequencing as previously reported. The mutation profiles of 62 primary conventional squamous cell carcinomas excluding other histologic variants are analyzed here. Associations were tested by Fisher exact test or Mann-Whitney U test as appropriate. P less than .1 was considered to be significant. Mutations in NLRP genes encoding pyrin-containing NLR proteins were exclusively identified in advanced stage HNSCC. These mutations were clustered at the leucine rich repeats region of pyrin-NLRs; and affected NLRP genes are mostly localized at chromosomes 11p15.4 and 19q13.42-19q13.43. Carcinomas that harbor these mutations demonstrated significantly higher mutation rates (P = .009). Clinically, NLRP mutations affected both genders equally, and these mutations were more frequently found in SCC arising in the floor of mouth (P = .034). Genome mutation rate is an important parameter for evaluating cancer cell genome instability. The identification of Young Investigator Awards Program Abstracts