Amplification of DNA Sequences from Chromosome 19q13.1 in Human Pancreatic Cell Lines

Conventional cytogenetics and comparative genomic hybridization (CGH) were utilized to identify recurrent chromosomal imbalances in 12 pancreatic adenocarcinoma cell lines. Multiple deletions and gains were observed in all cell lines. Losses affecting chromosomes or chromosome arms 9p, 13, 18q, 8p, 4, and 10p and gains involving chromosome arms or bands 19q13.1, 20q, 5p, 7p, 11q, 3q25–qter, 8q24, and 10q were commonly observed. Interestingly, 19 distinct sites of high-level amplification were found by CGH. Recurrent sites involved 19q13.1 (6 cases), 5p (3 cases), and 12p and 16p (2 cases). Amplification ofKRAS2was demonstrated in 2 cell lines and that ofERBB2in another. To define the occurrence of chromosome 19 amplification further, two-dimensional analysis ofNotI genomic restriction digests and fluorescencein situhybridization using probes from band 19q13.1 were utilized. High-level amplification of overlapping sets of chromosome 19NotI fragments was exhibited in 3 cell lines of which 2 showed amplification of bothOZFandAKT2genes and 1 that ofAKT2alone. In these 3 cell lines, amplification of chromosome 19 sequences was associated with the presence of a homogeneously staining region. Our results provide evidence of heterogeneity in the extent of chromosome 19 amplification and suggest the existence of yet unknown amplified genes that may play a role in pancreatic carcinogenesis.