Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN, MET, WNT2, and ERBB2.
Gastric adenocarcinoma is a malignant tumor with a high incidence and a low survival rate. In order to identify genetic alterations associated with this tumor, we screened 23 gastric adenocarcinomas for recurrent chromosomal imbalances by using comparative genomic hybridization (CGH). The most common gains of chromosomal material were found on chromosome arms 20q (10 cases), 16p (7 cases), and 1q (4 cases) and on chromosome 11 (4 cases). Losses were observed on chromosome arms 4q, 5q, 9p, and 21q (3 cases each). Four tumors exhibited high-level amplifications localized on chromosome regions 2p23-p24, 7q31-q32, 8p21-p22, 10q25-q26, 11q13, 17q11-q21, and 20q. Based on the position of these amplifications, candidate (onco)genes were selected and subsequently tested by Southern blot analysis of the respective tumors. Of the seven tested candidates, MYCN, MET, WNT2, and ERBB2 were found to participate in the amplicons of the respective tumor samples. Of these four presumably activated oncogenes, two, MYCN and WNT2, were previously not assumed to play a pathogenic role in stomach cancer. Among the other regions of imbalance, gain of 20q seems particularly interesting, because it is found in almost half of the analyzed cases and is highly amplified. Our data allowed us to narrow the relevant region down to the commonly gained bands 20q12-q13.1. This and other imbalanced regions provide a basis for searching new putative oncogenes and tumor suppressor genes involved in the development or progression of gastric adenocarcinoma.
Nessling
M
M
Abteilung Organisation komplexer Genome, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Solinas-Toldo
S
S
Wilgenbus
K K
KK
Borchard
F
F
Lichter
P
P
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D002874:Chromosome Mapping; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D018734:Genes, erbB-2 / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D051154:Wnt2 Protein
D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D051154:Wnt2 Protein