title: Genome profiling of pancreatic adenocarcinoma.
abstract: Pancreatic adenocarcinoma is one of the most aggressive human cancers. It displays many different chromosomal abnormalities and mutations. By using 244 K high-resolution array-comparative genomic hybridization (aCGH) we studied the genome alterations of 39 fine-needle aspirations from pancreatic adenocarcinoma and eight human adenocarcinoma pancreatic cell lines. Using both visual inspection and GISTIC analysis, recurrent losses were observed on 1p, 3p, 4p, 6, 8p, 9, 10, 11q, 15q, 17, 18, 19p, 20p, 21, and 22 and comprised several known or suspected tumor suppressor genes such as ARHGEF10, ARID1A, CDKN2A/B, FHIT, PTEN, RB1, RUNX1-3, SMAD4, STK11/LKB1, TP53, and TUSC3. Heterozygous deletion of the 1p35-p36 chromosomal region was identified in one-third of the tumors and three of the cell lines. This region, commonly deleted in human cancers, contains several tumor suppressor genes including ARID1A and RUNX3. We identified frequent genetic gains on chromosome arms 1q, 3q, 5p, 6p, 7q, 8q, 12q, 15q, 18q, 19q, and 20q. Amplifications were observed in 16 tumors. AKT2, CCND3, CDK4, FOXA2, GATA6, MDM2, MYC, and SMURF1 genes were gained or amplified. The most obvious amplification was located at 18q11.2 and targeted the GATA6 gene, which plays a predominant role in the initial specification of the pancreas and in pancreatic cell type differentiation. In conclusion, we have identified novel biomarkers and potential therapeutic targets in pancreatic adenocarcinoma.
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, UMR891 Inserm, Institut Paoli-Calmettes, Marseille, France.
authors.forename: David J
authors.initials: DJ
authors.lastname: Birnbaum
authors.forename: José
authors.initials: J
authors.lastname: Adélaïde
authors.forename: Emilie
authors.initials: E
authors.lastname: Mamessier
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lagarde
authors.forename: Geneviève
authors.initials: G
authors.lastname: Monges
authors.forename: Frédéric
authors.initials: F
authors.lastname: Viret
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalvès
authors.forename: Olivier
authors.initials: O
authors.lastname: Turrini
authors.forename: Jean-Robert
authors.initials: JR
authors.lastname: Delpero
authors.forename: Juan
authors.initials: J
authors.lastname: Iovanna
authors.forename: Marc
authors.initials: M
authors.lastname: Giovannini
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D044963:Biopsy, Fine-Needle; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion
chemical_list: D014408:Biomarkers, Tumor