Oligonucleotide array comparative genomic hybridization refines the structure of 8p23.1, 17q12 and 20q13.2 amplifications in gastric carcinomas.
Oligonucleotide array comparative genomic hybridization (aCGH) was applied on fifteen gastric cancer (GCA) samples to reveal information of DNA copy number changes at an exon-level resolution. Twelve of the samples represented the intestinal (IGCA) and three the diffuse (DGCA) type of GCA. The samples had previously been assessed for genetic stability by microsatellite analysis and categorized into microsatellite phenotypes according to the type of alterations. As compared to our previous results obtained using cDNA platforms, the oligonucleotide platforms revealed more aberrations per sample (0-45 vs. 0-22). A total of 22 amplifications were detected by the oligonucleotide arrays. Ten of the amplicons had also been detected on the cDNA platform, but five of them spanned only one or a few cDNA clones, thus resembling apparent outliers. Two tumors showed five or more amplifications by oligonucleotide aCGH, suggesting the presence of an amplifier phenotype. The amplifications occurred irrespective of the microsatellite phenotypes. None of the DGCA tumors showed more than one aberration, whereas the IGCA tumors showed several aberrations. The increased resolution of the oligonucleotide arrays enabled the detection of amplicon boundaries at gene level, allowing, e.g., the determination of the 17q12 core amplicon and interstitial losses within the 8p23.1-->p22 and 20q13.2-->q13.1 amplifications. Previously no losses have been reported within amplified regions in GCA. In addition to novel amplified regions, the oligonucleotide array results describe novel targets for amplicons at 8p11 (SFRP1), 11p12 (LRRC4C), and 19q13.2 (CEACAM6).
Vauhkonen
H
H
Department of Pathology, Haartman Institute, University of Helsinki, Finland. hanna.vauhkonen@helsinki.fi
Vauhkonen
M
M
Sipponen
P
P
Knuutila
S
S
D000368:Aged; D000369:Aged, 80 and over; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013274:Stomach Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology