Gene expression alterations over large chromosomal regions in cancers include multiple genes unrelated to malignant progression

被引:44
作者
Masayesva, BG
Ha, P
Garrett-Mayer, E
Pilkington, T
Mao, R
Pevsner, J
Speed, T
Benoit, N
Moon, CS
Sidransky, D
Westra, WH
Califano, J
机构
[1] Johns Hopkins Med Inst, Dept Otolaryngol, Baltimore, MD 21205 USA
[2] Johns Hopkins Med Inst, Dept Head & Neck Surg, Head & Neck Canc Res Div, Baltimore, MD 21205 USA
[3] Johns Hopkins Med Inst, Dept Oncol Biostat, Baltimore, MD 21205 USA
[4] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA
[5] Kennedy Krieger Inst, Dept Neurol, Baltimore, MD 21205 USA
[6] Bates Coll, Lewiston, ME 04240 USA
关键词
chromosomal; mapping; microarrays; comparative genomic hybridization; allelic imbalance; head and neck squamous cell carcinoma;
D O I
10.1073/pnas.0400027101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:8715 / 8720
页数:6
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