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 pancr eatic adenocarcinoma cell lines. Multiple deletions and gains were obs erved in all cell lines. Losses affecting chromosomes or chromosome ar ms 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 commonl y observed. Interestingly, 19 distinct sites of high-level amplificati on were found by CGH. Recurrent sites involved 19q13.1 (6 cases), 5p ( 3 cases), and 12p and 16p (2 cases). Amplification of KRAS2 was demons trated in 2 cell lines and that of ERBB2 in another. To define the occ urrence of chromosome 19 amplification further, two-dimensional analys is of NotI genomic restriction digests and fluorescence in situ hybrid ization using probes from band 19q13.1 were utilized. High-level ampli fication of overlapping sets of chromosome 19 NotI fragments was exhib ited in 3 cell lines of which 2 showed amplification of both OZF and A KT2 genes and 1 that of AKT2 alone. In these 3 cell lines, amplificati on of chromosome 19 sequences was associated with the presence of a ho mogeneously staining region, Our results provide evidence of heterogen eity in. the extent of chromosome 19 amplification and suggest the exi stence of yet unknown amplified genes that may play a role in pancreat ic carcinogenesis. (C) 1998 Academic Press.