DNA Copy Number Changes and Evaluation of MYC, IGF1R, and FES Amplification in Xenografts of Pancreatic Adenocarcinoma

Abstract

We analyzed eight samples of xenografted human pancreatic tumors and two metastases developed in mice by comparative genomic hybridization (CGH). The most recurrent changes were: gains on chromosomes 8 (8q24 ∼qter; 7/8 cases), 15 (15q25 ∼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 ∼q21 and 6q24 ∼qter; 5/8 cases each), and 9 (9p23 ∼pter; 5/8 cases). The two metastases maintained the aberrations of the original pancreatic tumor plus gain of 11q12 ∼q13 and 22q. Loss of heterozygosity analysis was carried out for 10p14 ∼pter, a region that was lost in 3/8 samples. All of them presented allelic imbalance for all the informative loci. Fluorescence in situ hybridization and Southern analysis were performed to test some candidate oncogenes in 8q24 (MYC) and 15q25 ∼qter ( IGF1R and FES). Two of seven tumors showed high-level amplification of MYC relative to the centromere ( >3-fold), another two tumors had low-level amplification (1.5- to 3.0-fold), and one displayed 5.5 MYC signals/cell. In relation to the FES gene, low-level amplification was found in three tumors. Southern 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 progression or other genes located in these regions are responsible for the amplifications found by CGH.