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 of KRAS2 was demonstrated in 2 cell lines and that of ERBB2 in another. To define the occurrence of chromosome 19 amplification further, two-dimensional analysis of NotI genomic restriction digests and fluorescence in situ hybridization using probes from band 19q13.1 were utilized. High-level amplification of overlapping sets of chromosome 19 NotI fragments was exhibited in 3 cell lines of which 2 showed amplification of both OZF and AKT2 genes and 1 that of AKT2 alone. 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.
Curtis
L J
LJ
Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
Li
Y
Y
Gerbault-Seureau
M
M
Kuick
R
R
Dutrillaux
A M
AM
Goubin
G
G
Fawcett
J
J
Cram
S
S
Dutrillaux
B
B
Hanash
S
S
Muleris
M
M
D002869:Chromosome Aberrations / Q000235:genetics*; D002871:Chromosome Banding; D025063:Chromosome Disorders; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D015342:DNA Probes / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005784:Gene Amplification / Q000235:genetics*; D052138:Genes, Neoplasm; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D010190:Pancreatic Neoplasms / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D015252:Deoxyribonucleases, Type II Site-Specific; C038565:GCGGCCGC-specific type II deoxyribonucleases