title: High resolution analysis of DNA copy-number aberrations of chromosomes 8, 13, and 20 in gastric cancers.
abstract: DNA copy-number gains of chromosomes 8q, 13q, and 20q are frequently observed in gastric cancers. Moreover gain of chromosome 20q has been associated with lymph node metastasis. The aim of this study was to correlate DNA copy-number changes of individual genes on chromosomes 8q, 13q, and 20q in gastric adenocarcinomas to clinicopathological data. DNA isolated from 63 formalin-fixed and paraffin-embedded gastric adenocarcinoma tissue samples was analyzed by whole-genome microarray comparative genomic hybridization and by multiplex ligation-dependent probe amplification (MLPA), targeting 58 individual genes on chromosomes 8, 13, and 20. Using array comparative genomic hybridization, gains on 8q, 13q, and 20q were observed in 49 (77.8%), 25 (39.7%), and 49 (77.8%) gastric adenocarcinomas, respectively. Gain of chromosome 20q was significantly correlated with lymph node metastases (p = 0.05) and histological type (p = 0.02). MLPA revealed several genes to be frequently gained in DNA copy number. The oncogene c-myc on 8q was gained in 73% of the cancers, while FOXO1A and ATP7B on 13q were both gained in 28.6% of the cases. Multiple genes on chromosome 20q showed gains in more than 60% of the cancers. DNA copy-number gains of TNFRSF6B (20q13.3) and ZNF217 (20q13.2) were significantly associated with lymph node metastasis (p = 0.02) and histological type (p = 0.02), respectively. In summary, gains of chromosomes 8q, 13q, and 20q in gastric adenocarcinomas harbor DNA copy-number gains of known and putative oncogenes. ZNF217 and TNFRSF6B are associated with important clinicopathological variables, including lymph node status.
authors.affiliation: Department of Pathology, VU University Medical Center, PO Box 7057, 1007, Amsterdam, The Netherlands.
authors.forename: Tineke E
authors.initials: TE
authors.lastname: Buffart
authors.forename: Nicole C T
authors.initials: NC
authors.lastname: van Grieken
authors.forename: Marianne
authors.initials: M
authors.lastname: Tijssen
authors.forename: Jordy
authors.initials: J
authors.lastname: Coffa
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.forename: Heike I
authors.initials: HI
authors.lastname: Grabsch
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Beatriz
authors.initials: B
authors.lastname: Carvalho
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13; D002890:Chromosomes, Human, Pair 20; D002898:Chromosomes, Human, Pair 8; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*; D051438:Syntaxin 16 / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
chemical_list: D053323:Receptors, Tumor Necrosis Factor, Member 6b; C496118:STX16 protein, human; D051438:Syntaxin 16; C505911:TNFRSF6B protein, human; D015534:Trans-Activators; C113698:ZNF217 protein, human
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