Molecular analysis of Tumor Suppressor genes in synchronous and metachronous secondary carcinomas of the upper aerodigestive tract. R. Birkenhager, W. Maier, G. Ridder, R. Laszig, J. Schipper. Otorhinolaryngology H&N Surg, Univ Freiburg, Freiburg, GermanyDep. ORL&HN Surg, Medical School, University of Freiburg, Killianstrasse 5, D-79106 Freiburg, Germany.
   Genomic instability, reflecting the propensity and the susceptibility of the genome to acquire multiple alterations, might be considered a driving force behind multiple carcinogenesis. Head-and-neck cancer (HNC) patients have a risk of 10-15 % of developing second tumors of the upper aerodigestive tract. Due to the identical histological tumor entity of secondary carcinomas, their appearance cannot be explained exclusively by somatic mutations. Therefore an additional genomic predisposition for the development of synchronous and metachronous secondary carcinomas of the upper aerodigestive tract by this patient collective must be postulated. The genetic reason for this appearance of this special type of secondary carcinomas on genomic level has not been analyzed and investigated up to now. This patient collective demonstrates an inimitably homogenous gene pool for the analysis for such genomic predisposition. In our project we investigated a group of clinically consistently characterized patients who developed synchronous or metachronous secondary carcinomas of the mucosa in the upper aerodigestive tract with a SNP array-based analysis. By utilizing the Affymetrix GeneChip Chromosome Copy Number Tool, the allelic imbalance profiles on genomic level of these patients with secondary tumors were generated based on 10 K and 100 K XbaI/HindIII SNP mapping array. With this method it was possible to identify different loss of heterozygosity (LOH) areas specially on chromosome one and six. The aim of our project is to analyze the whole genomic background of these patients for identification of genomic alterations loss of LOH's areas and suppressor genes, responsible for the development of this special kind of secondary tumors in the upper aerodigestive tract.