Genetic differences in endocrine pancreatic tumor subtypes detected by comparative genomic hybridization

The molecular pathogenesis as well as histogenesis of endocrine pancreatic tumors (EPTs) is not well understood, and the clinical behavior of EPTs is difficult to predict using current morphological criteria. Thus, more accur ate markers of risk and better understanding of tumor initiation and progre ssion are needed to allow a precise classification of EPTs. We have studied 44 benign and malignant EPTs by comparative genomic hybridization to corre late the overall number of genetic alterations with clinical and histopatho logical parameters and to identify chromosomal regions which might harbor g enes involved in EPT pathogenesis and progression, Aberrations were found i n 36 EPTs, and chromosomal losses (mean, 5.3) were slightly more frequent t han gains (mean, 4.6), The most frequent losses involved Y (45% of male EPT s), 6q (39%), 11q (36%), 3p, 3q, 11p (each 30%), 6p (27%), and 10q and Xq ( each 25%), whereas most common gains included 7q (43%), 17q (41%), 5q and 1 4q teach 32%), 7p, 9q, 17p, 20q (each 27%), and 12q and Xp (each 25%), A co rrelation was found between the total number of genetic changes per tumor a nd both tumor size and disease stage. In particular, losses of 3p and 6 and gains of 14q and Xq were found to be associated with metastatic disease. F urthermore, characteristic patterns of genetic changes were found in the va rious EPT subtypes, eg, 6q loss in malignant insulinomas, indicating that t hese groups might evolve along genetically different pathways. The highligh ted genetic aberrations, including the newly found involvement of 6q losses and sex chromosome alterations, should stimulate the further analysis of t hese chromosomal regions, which may lead to the discovery of novel genes im portant in the tumorigenesis and evolution of EPTs.