TY - JOUR
T1 - Clustering of Molecular Alterations in Gastroesophageal Carcinomas
AU - Koon, Natalie
AU - Zaika, Alexander
AU - Moskaluk, Christopher A.
AU - Frierson, Henry F.
AU - Knuutila, Sakari
AU - Powell, Steven M.
AU - El-Rifai, Wa'El
N1 - Funding Information:
Address all correspondence to: Wa’el El-Rifai, MD, PhD. Digestive Health Center of Excellence, University of Virginia Health System, PO Box 800708, Charlottesville, VA 22908-0708, USA. E-mail: [email protected] 1This work was supported by a grant award from the National Cancer Institute (1 R01 CA106176 to W.E.R.) and by the Cancer Center and Research and Development funds at the University of Virginia. The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute or the University of Virginia. Received 7 October 2003; Revised 11 November 2003; Accepted 19 November 2003.
PY - 2004
Y1 - 2004
N2 - Gene expression levels are regulated at many levels. Integration of genome-wide analyses for the study of DNA and RNA provides a unique tool to detect genetic alterations in the cancer genome. In this study, we generated and integrated DNA amplification data from comparative genomic hybridization (CGH) and serial analyses of gene expression (SAGE) in order to obtain a molecular profile of gastroesophageal junction (GEJ) carcinomas. DNA amplifications mapped to specific chromosomal regions and were frequently seen at 1q, 4q, 5q, 6p, 7p, 8q, 17q, and 20q. Using SAGE, we obtained over 156,432 tags from GEJ adenocarcinomas and normal gastric mucosa. These tags were assigned to UniGene clusters. Chromosomal positions for overexpressed genes were obtained to produce a GEJ carcinoma transcriptome map. A total of 123 genes was significantly overexpressed (more than fivefold; P<.01) in one or more SAGE libraries. This gene overexpression map was integrated and compared to the chromosomal CGH ideogram. Several chromosomal arms that had frequent DNA amplifications showed frequent gene expression alterations such as chromosomes 1 (15 genes), 2 (9 genes), 6 (6 genes), 11 (6 genes), 12 (8 genes), and 17 (13 genes). Despite the relatively large DNA amplification regions, overexpressed genes frequently mapped and clustered to small chromosomal regions at early-replicating (Giemsa light) bands such as 1q21.3 (nine genes), 6p21.3 (five genes), and 17q21 (eight genes). These results provide a comprehensive tool to search for DNA amplifications and overexpressed genes in GEJ carcinoma. The observed phenomenon of the presence of large amplification areas, yet clustering of overexpressed genes to relatively small loci, may suggest a high organization of chromatin and cancer-related genes in the nucleus.
AB - Gene expression levels are regulated at many levels. Integration of genome-wide analyses for the study of DNA and RNA provides a unique tool to detect genetic alterations in the cancer genome. In this study, we generated and integrated DNA amplification data from comparative genomic hybridization (CGH) and serial analyses of gene expression (SAGE) in order to obtain a molecular profile of gastroesophageal junction (GEJ) carcinomas. DNA amplifications mapped to specific chromosomal regions and were frequently seen at 1q, 4q, 5q, 6p, 7p, 8q, 17q, and 20q. Using SAGE, we obtained over 156,432 tags from GEJ adenocarcinomas and normal gastric mucosa. These tags were assigned to UniGene clusters. Chromosomal positions for overexpressed genes were obtained to produce a GEJ carcinoma transcriptome map. A total of 123 genes was significantly overexpressed (more than fivefold; P<.01) in one or more SAGE libraries. This gene overexpression map was integrated and compared to the chromosomal CGH ideogram. Several chromosomal arms that had frequent DNA amplifications showed frequent gene expression alterations such as chromosomes 1 (15 genes), 2 (9 genes), 6 (6 genes), 11 (6 genes), 12 (8 genes), and 17 (13 genes). Despite the relatively large DNA amplification regions, overexpressed genes frequently mapped and clustered to small chromosomal regions at early-replicating (Giemsa light) bands such as 1q21.3 (nine genes), 6p21.3 (five genes), and 17q21 (eight genes). These results provide a comprehensive tool to search for DNA amplifications and overexpressed genes in GEJ carcinoma. The observed phenomenon of the presence of large amplification areas, yet clustering of overexpressed genes to relatively small loci, may suggest a high organization of chromatin and cancer-related genes in the nucleus.
KW - Comparative genomic hybridization
KW - Gastroesophageal junction cancer
KW - Gene clustering
KW - Serial analysis of gene expression
KW - Transcriptome analyses
UR - http://www.scopus.com/inward/record.url?scp=2142751576&partnerID=8YFLogxK
U2 - 10.1593/neo.03385
DO - 10.1593/neo.03385
M3 - Article
C2 - 15140403
AN - SCOPUS:2142751576
SN - 1522-8002
VL - 6
SP - 143
EP - 149
JO - Neoplasia
JF - Neoplasia
IS - 2
ER -