Genetic profiles of gastroesophageal cancer: combined analysis using expression array and tiling array--comparative genomic hybridization.
We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas by means of 32k high-resolution array-based comparative genomic hybridization and 27k oligo gene expression arrays, and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-23, 5p15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction, with upregulation in one quarter of the tumors. Gains/losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can be applied to adenocarcinomas of the distal esophagus and gastroesophageal junction alike.
Isinger-Ekstrand
Anna
A
Department of Oncology, Clinical Sciences, Lund University, Barngatan 2b, Lund, Sweden. anna.ekstrand@med.lu.se
Johansson
Jan
J
Ohlsson
Mattias
M
Francis
Princy
P
Staaf
Johan
J
Jönsson
Mats
M
Borg
Ake
A
Nilbert
Mef
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055028:Comparative Genomic Hybridization / Q000379:methods*; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics*; D004943:Esophagogastric Junction; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D013274:Stomach Neoplasms / Q000235:genetics*
D066246:ErbB Receptors; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6