Putative tumor suppressor loci at 6q22 and 6q23-q24 are involved in the malignant progression of sporadic endocrine pancreatic tumors

Our previous comparative genomic hybridization study on sporadic endocrine pancreatic tumors (EPTs) revealed frequent losses on chromosomes 11q, 3p, a nd 6q, The aim of this study was to evaluate the importance of 6q losses in the oncogenesis of sporadic EPTs and to narrow down the smallest regions o f allelic deletion. A multimodal approach com bining polymerase chain react ion-based allelotyping, double-target fluorescence in situ hybridization, a nd comparative genomic hybridization was used in a collection of 109 sporad ic EPTs from 93 patients. Nine polymorphic microsatellite markers (6q13 to 6q25q27) were investigated, demonstrating a loss of heterozygosity (LOH) in 62.2% of the patients. A LOH was significantly more common in tumors >2 cm in diameter than below this threshold as well as in malignant than in beni gn tumors. We were able to narrow down the smallest regions of allelic dele tion at 6q22.1 (D6S262) and 6q23-q24 (D6S310-UTRN) with LOH-frequencies of 50.0% and 41.2 to 56.3%, respectively. Several promising tumor suppressor c andidates are located in these regions, Additional fluorescence in situ hyb ridization analysis on 46 EPTs using three locus-specific probes (6q21, 6q2 2, and 6q27) as well as a centromere 6-specific probe revealed complete los s of chromosome 6 especially in metastatic disease, We conclude that the tw o hot spots found on 6q may harbor putative tumor suppressor genes involved not only in the oncogenesis but maybe also in the malignant and metastatic progression of sporadic EPTs.