Genomic DNA-Chip Hybridization Reveals a Higher Incidence of Genomic Amplifications in Pancreatic Cancer than Conventional Comparative Genomic Hybridization and Leads to the Identification of Novel Candidate Genes

• Published in: Cancer research (Chicago, Ill.) Vol. 64; no. 13; pp. 4428 - 4433
• Main Authors: Holzmann, Karlheinz, Kohlhammer, Holger, Schwaenen, Carsten, Wessendorf, Swen, Kestler, Hans A., Schwoerer, Alexandra, Rau, Bettina, Radlwimmer, Bernd, Döhner, Hartmut, Lichter, Peter, Gress, Thomas, Bentz, Martin
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.07.2004
• Subjects: Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Cell Line, Tumor; Chromosomes, Human, Pair 11 - genetics; Chromosomes, Human, Pair 20 - genetics; Consensus Sequence; Cyclin D1 - genetics; ErbB Receptors - genetics; Female; Gene Amplification; Humans; In Situ Hybridization, Fluorescence - methods; Liver Neoplasms - genetics; Liver Neoplasms - secondary; Male; MAP Kinase Kinase Kinases; Medical sciences; Middle Aged; Mitogen-Activated Protein Kinase Kinase Kinase 11; Nucleic Acid Hybridization - methods; Oligonucleotide Array Sequence Analysis; Pancreatic Neoplasms - genetics; Pharmacology. Drug treatments; Polymerase Chain Reaction - methods; Protein Serine-Threonine Kinases - genetics; Trans-Activators - genetics; Tumors; Gene amplification; Comparative genomic hybridization; DNA chip; Pancreas cancer; Digestive diseases; Chromosome DNA; Candidate gene; Malignant tumor; Gene expression; Genome; Pancreatic disease; Incidence
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-04-0431

Genomic analyses aimed at the detection of high-level DNA amplifications were performed on 13 widely used pancreatic cancer cell lines and 6 pancreatic tumor specimens. For these analyses, array-based comparative genomic hybridization (Matrix-CGH) onto dedicated microarrays was used. In comparison with chromosomal CGH (eight amplifications), a >3-fold number of DNA amplifications was detected (n = 29). The most frequent amplifications mapped to 7p12.3 (three pancreatic cancer cell lines and three pancreatic tumor specimens), 8q24 (four pancreatic cancer cell lines and one pancreatic tumor specimen), 11q13 (three pancreatic cancer cell lines and three pancreatic tumor specimens), and 20q13 (four pancreatic cancer cell lines and three pancreatic tumor specimens). Genes contained in the consensus regions were MYC (8q24), EGFR (7p12.3), and FGF3 (11q13). In six of seven pancreatic cancer cell lines and pancreatic tumor specimens with 20q13 amplifications, the novel candidate gene NFAT C2, which plays a role in the activation of cytokines, was amplified. Other amplifications also affected genes for which a pathogenetic role in pancreatic carcinoma has not been described, such as BCL10 and BCL6, two members of the BCL family. A subset of amplified genes was checked for overexpression by means of real-time PCR, revealing the highest expression levels for BCL6 and BCL10. Thus, Matrix-CGH allows the detection of a high number of amplifications, resulting in the identification of novel candidate genes in pancreatic cancer.