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 EPTs, we analyzed 17 paired specimens of primary EPTs and their metastases and 28 nonmetastatic EPTs using comparative genomic hybridization (CGH). Genomic alterations 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 metastases, 12.5 in their primary tumors, and 4.5 in nonmetastatic EPTs. Statistical analysis of shared genomic changes in matched pairs of primary tumors and metastases showed a high probability (>95%) of a clonal relationship in 15 of the 17 cases. A closely related genetic pattern was also demonstrated on the basis of concordance analysis of the two groups. The most striking genomic changes which were enriched in metastases included gains of chromosomes 4 and 7 and losses of 21q. Other common regions of frequent losses (>40%) identified in metastases and/or their primary tumors involved 2p, 2q, 3p, 3q, 6q, 10p, and 11p, whereas frequently detected gains (>40%) in the paired tumors involved 5p, 5q, 12q, 14q, 17q, 18q, and 20q. These chromosomal aberrations were found in significantly fewer nonmetastatic EPTs. Some of these chromosomal loci may harbor genes contributing to the progression of EPT.
Zhao
J
J
Department of Pathology, University of Zurich, Zurich, Switzerland. jianming.zhao@pty.usz.ch
Moch
H
H
Scheidweiler
A F
AF
Baer
A
A
Schäffer
A A
AA
Speel
E J
EJ
Roth
J
J
Heitz
P U
PU
Komminoth
P
P
D007516:Adenoma, Islet Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance / Q000235:genetics*; D002648:Child; D002999:Clone Cells; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010190:Pancreatic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D011336:Probability