Genomic array and expression analysis of frequent high-level amplifications in adenocarcinomas of the gastro-esophageal junction.
Adenocarcinomas of the gastroesophageal junction (GEJ) show frequent high-level amplifications (HLA), but the underlying genes are not well defined. We have characterized genomic gain in 14 GEJ carcinomas by array-based comparative genomic hybridization (aCGH). The most frequent gains and amplifications were detected at 7q (57%), 8q (57%), 17q (64%), and 20q (79%), with minimally amplified regions at 7q21.1, 8q24.2, 17q12, and 20q13.2. Five HLA were detected on 7q, one on 8q, two on 17q, and three on 20q. HLA of 8q24 and 17q12 were related to MYC and ERBB2, respectively. The HLA on 7q21 was associated recurrently with ABCB1, whereas the amplified region on 20q13 implicated ZNF217, BCAS1, and CYP24. RNA expression analysis of 11 adenocarcinomas by reverse-transcription polymerase chain reaction was performed for cancer-related genes residing at 7q21 (ABCB1, ABCB4, CDK6, HGF, DMTF1, SRI, TP53AP1) and 20q13 (ZNF217, BCAS1, CYP24, TNFRSF6B). The most frequently upregulated gene on 7q21 was HGF (45%), but there was no association with genomic amplification. The most frequently overexpressed gene at 20q13 was BCAS1 (27%), which was related to HLA of this region (P = 0.006) in all three cases. We conclude that HLA occur often in GEJ adenocarcinomas. The gene responsible for the HLA of 7q21 requires further investigation, whereas BCAS1 is a good candidate for the frequent amplification of 20q13.
van Dekken
Herman
H
Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands. h.vandekken@erasmusmc.nl
Vissers
Kees
K
Tilanus
Hugo W
HW
Kuo
Wen L
WL
Tanke
Hans J
HJ
Rosenberg
Carla
C
Ijszenga
Marije
M
Szuhai
Karoly
K
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger