Genomic imbalances in the progression of endocrine pancreatic tumors

Endocrine pancreatic tumors (EPTs) are neoplasms with malignant potential. To explore the molecular basis of metastatic progression in human El we ana lyzed 17 paired specimens of primary EPTs and their metastases and 28 nonme tastatic EPTs using comparative genomic hybridization (CGH). Genomic altera tions were detected in all of the matched primary/metastatic tumors and 19 (58%) nonmetastatic EPTs. The mean number of genomic changes was 17.3 in me tastases, 12.5 in their primary tumors, and 4.5 in nonmetastatic EPTs. Stat istical analysis of shared genomic changes in matched pairs of primary tumo rs and metastases showed a high probability (>95%) of a clonal relationship in 15 of the 17 cases. A closely related genetic pattern was also demonstr ated on the basis of concordance analysis of the two groups. The most strik ing genomic changes which were enriched in metastases included gains of chr omosomes 4 and 7 and losses of 21q. Other common regions of frequent losses (>40%) identified in metastases and/or their primary tumors involved 2p, 2 q, 3p, 3q, 6q, 10p, and 11p, whereas frequently detected gains (>40%) in th e paired tumors involved 5p, 5q, 12q, 14q, 17q, 18q, and 20q. These chromos omal aberrations were found in significantly fewer nonmetastatic EPTs. Some of these chromosomal loci may harbor genes contributing to the progression of El (C) 2001 Wiley-Liss, Inc.