Gene expression alterations over large chromosomal regions in cancers include multiple genes unrelated to malignant progression.
In solid tumors, the relationship between DNA copy number and global expression over large chromosomal regions has not been systematically explored. We used a 12,626-gene expression array analysis of head and neck squamous cell carcinoma and normal oral mucosa and annotated gene expression levels to specific chromosomal loci. Expression alterations correlated with reported data using comparative genomic hybridization. When genes with significant differences in expression between normal and malignant lesions, as defined by significance analysis of microarrays (SAM), were compared to nonsignificant genes, similar chromosomal patterns of alteration in expression were noted. Individual tumors underwent microsatellite analysis and chi(2) analysis of expression at 3p and 22q. Significant 3p underexpression and 22q overexpression were found in all primary tumors with 3p and 22q allelic imbalance, respectively, whereas no tumor without allelic imbalance on these chromosomal arms demonstrated expression differences. Loss and gain of chromosomal material in solid cancers can alter gene expression over large chromosomal regions, including multiple genes unrelated to malignant progression.
Masayesva
Brett G
BG
Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Ha
Patrick
P
Garrett-Mayer
Elizabeth
E
Pilkington
Thomas
T
Mao
Rong
R
Pevsner
Jonathan
J
Speed
Traci
T
Benoit
Nicole
N
Moon
Chul-So
CS
Sidransky
David
D
Westra
William H
WH
Califano
Joseph
J
D022981:Allelic Imbalance; D016022:Case-Control Studies; D002877:Chromosomes, Human / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*
D004273:DNA, Neoplasm