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Genome profiling of pancreatic adenocarcinoma
Author(s) -
Birnbaum David J.,
Adélaïde José,
Mamessier Emilie,
Finetti Pascal,
Lagarde Arnaud,
Monges Geneviève,
Viret Frédéric,
Gonçalvès Anthony,
Turrini Olivier,
Delpero JeanRobert,
Iovanna Juan,
Giovannini Marc,
Birnbaum Daniel,
Chaffanet Max
Publication year - 2011
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20870
Subject(s) - cdkn2a , cancer research , adenocarcinoma , fhit , comparative genomic hybridization , biology , tumor suppressor gene , pancreas , gene , genetics , chromosome , carcinogenesis , cancer , biochemistry
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. © 2011 Wiley‐Liss, Inc.