DNA copy number changes and evaluation of MYC, IGF1R, and FES amplification in xenografts of pancreatic adenocarcinoma

We analyzed eight samples of xenografted human pancreatic tumors and two me tastases developed in mice by comparative genomic hybridization (CGH). The most recurrent changes were: gains on chromosomes 8 (8q24 similar to qter; 7/8 cases), 15 (15q25 similar to q26; 6/8 cases), 16 (16p in 6/8 cases; 16q in 5/8 cases), 20 (20q; 6/8 cases), and 19 (19q; 5/8 cases); and losses on chromosomes 18 (18q21; 6/8 cases), 6 (6q16 similar to q21 and 6q24 similar to qter; 5/8 cases each), and 9 (9p23 similar to pter; 5/8 cases). The two metastases maintained the aberrations of the original pancreatic tumor plu s gain of 11q12 similar to q13 and 22q. Loss of heterozygosity analysis was carried out for 10p14 similar to pter, a region that was lost in 3/8 sampl es. All of them presented allelic imbalance for all the informative loci. F luorescence in situ hybridization and Southern analysis were performed to t est some candidate oncogenes in 8q24 (MYC) and 15q25 similar to qter (IGF1R and FES). Two of seven tumors showed high-level amplification of MYC relat ive to the centromere (>3-fold), another two tumors had low-level amplifica tion (1.5- to 3.0-fold), and one displayed 5.5 MYC signals/cell. In relatio n to the FES gene, low-level amplification was found in three tumors. South ern analysis showed five cases with a low-level amplification of IGF1R. Our data suggest that either few extra gene copies may be enough for cancer pr ogression or other genes located in these regions are responsible for the a mplifications found by CGH. (C) Elsevier Science Inc., 1999. All rights res erved.