Abstract 2104: Molecular alterations in JAK1 and JAK2 genes in head and neck squamous cell carcinoma

Abstract

Abstract Among the ten most common cancers are the head and neck tumors, with more than 600,000 new cases diagnosed annually worldwide, the majority (90%) represented by the head and neck squamous cell carcinomas (HNSCC). Somatic mutations occur in the genomes of all dividing cells, both normal and neoplastic. The JAK-STAT signaling pathway controls important cell events such as survival, proliferation and differentiation. The presence of mutations in the phosphorylation dominion of protein kinases as JAK family have been linked to development of different kinds of tumors such as hematological, breast, lung and gastric cancers. Furthermore, inhibitors of protein kinases (Gefitinib and Erlotinib) have demonstrated a remarkable efficacy in treatment of some cancers. To date, we do not succeeded in finding reports linking mutations in members of the JAK-STAT pathway and HNSCC. Therefore it is necessary to plunge into molecular research that could identify failures in the cellular machinery with consequent discovery of potential molecular targets and drug direct delivered to them. The present work aims to evaluate the presence of mutations in the JAK-STAT signaling pathway members (JAK1 and JAK2) and verify the expression level of these genes in HNSCC samples. For the mutation detection, primers were designed to cDNA molecules and allowed the amplification of contiguous 700-bp fragments that cover the entire coding region of each gene. The JAK1 and JAK2 genes were investigated in 20 HNSCC samples and no mutation was detected. Polymorphisms were found in JAK1 at codons 193 (20%), 659 (5%), 683 (25%), 699 (10%), 733 (25%) and 1032 (20%) and in JAK2 codons 163 (60%), 830 (85%) and 1063 (5%). In addition we evaluated the expression level of these genes in 87 HNSCC samples and both were found downreguted in the majority of HNSCC samples (JAK1 in 82% and JAK2 in 81%). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2104. doi:1538-7445.AM2012-2104