PMID- 15221937 OWN - NLM STAT- MEDLINE DCOM- 20040827 LR - 20061115 IS - 0022-3417 (Print) IS - 0022-3417 (Linking) VI - 203 IP - 3 DP - 2004 Jul TI - Array-based comparative genomic hybridization for the detection of DNA sequence copy number changes in Barrett's adenocarcinoma. PG - 780-8 AB - Array-based comparative genomic hybridization (aCGH) allows the identification of DNA sequence copy number changes at high resolution by co-hybridizing differentially labelled test and control DNAs to a micro-array of genomic clones. The present study has analysed a series of 23 formalin-fixed, paraffin wax-embedded tissue samples of Barrett's adenocarcinoma (BCA, n = 18) and non-neoplastic squamous oesophageal (n = 2) and gastric cardia mucosa (n = 3) by aCGH. The micro-arrays used contained 287 genomic targets covering oncogenes, tumour suppressor genes, and DNA sequences localized within chromosomal regions previously reported to be altered in BCA. DNA sequence copy number changes for a panel of approximately 50 genes were identified, most of which have not been previously described in BCA. DNA sequence copy number gains (mean 41 +/- 25/BCA) were more frequent than DNA sequence copy number losses (mean 20 +/- 15/BCA). The highest frequencies for DNA sequence copy number gains were detected for SNRPN (61%); GNLY (44%); NME1 (44%); DDX15, ABCB1 (MDR), ATM, LAMA3, MYBL2, ZNF217, and TNFRSF6B (39% each); and MSH2, TERC, SERPINE1, AFM137XA11, IGF1R, and PTPN1 (33% each). DNA sequence copy number losses were identified for PDGFB (44%); D17S125 (39%); AKT3 (28%); and RASSFI, FHIT, CDKN2A (p16), and SAS (CDK4) (28% each). In all non-neoplastic tissue samples of squamous oesophageal and gastric cardia mucosa, the measured mean ratios were 1.00 (squamous oesophageal mucosa) or 1.01 (gastric mucosa), indicating that no DNA sequence copy number chances were present. For validation, the DNA sequence copy number changes of selected clones (SNRPN, CMYC, HER2, ZNF217) detected by aCGH were confirmed by fluorescence in situ hybridization (FISH). These data show the sensitivity of aCGH for the identification of DNA sequence copy number changes at high resolution in BCA. The newly identified genes may include so far unknown biomarkers in BCA and are therefore a starting point for further studies elucidating their possible role in Barrett's carcinogenesis. CI - Copyright 2004 Pathological Society of Great Britain and Ireland. FAU - Albrecht, Bettina AU - Albrecht B AD - University Hospital Freiburg, Institute of Pathology, Freiburg i Br, Germany. FAU - Hausmann, Michael AU - Hausmann M FAU - Zitzelsberger, Horst AU - Zitzelsberger H FAU - Stein, Hubert AU - Stein H FAU - Siewert, Jorg Rudiger AU - Siewert JR FAU - Hopt, Ulrich AU - Hopt U FAU - Langer, Rupert AU - Langer R FAU - Hofler, Heinz AU - Hofler H FAU - Werner, Martin AU - Werner M FAU - Walch, Axel AU - Walch A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Pathol JT - The Journal of pathology JID - 0204634 RN - 0 (DNA, Neoplasm) SB - IM MH - Adenocarcinoma/*genetics MH - Barrett Esophagus/*genetics MH - DNA, Neoplasm/*genetics MH - Esophageal Neoplasms/*genetics MH - Humans MH - In Situ Hybridization, Fluorescence/methods MH - Nucleic Acid Hybridization/methods MH - Oligonucleotide Array Sequence Analysis/methods MH - Precancerous Conditions/*genetics EDAT- 2004/06/29 05:00 MHDA- 2004/08/28 05:00 CRDT- 2004/06/29 05:00 PHST- 2004/06/29 05:00 [pubmed] PHST- 2004/08/28 05:00 [medline] PHST- 2004/06/29 05:00 [entrez] AID - 10.1002/path.1576 [doi] PST - ppublish SO - J Pathol. 2004 Jul;203(3):780-8. doi: 10.1002/path.1576.