Correlation between genomic DNA copy number alterations and transcriptional expression in hepatitis B virus-associated hepatocellular carcinoma.
Human hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, in which the genetic mechanisms of oncogenesis are still unclear. To investigate whether the genomic DNA copy number alterations may contribute to primary HCC, the cDNA microarray-based comparative genomic hybridization (CGH) analysis was here performed in 41 primary HCC infected by hepatitis B virus and 12 HCC cell lines. The resulting data showed that, on average, 7.25% of genome-wide DNA copy numbers was significantly altered in those samples (4.61+/-2.49% gained and 2.64+/-1.78% lost). Gains involving 1q, 6p, 8q and 9p were frequently observed in these cases; and whilst, losses involving Ip, 16q and 19p occurred in most patients. To address the correlation between the alteration of genomic DNA copy numbers and transcriptional expression, the same cDNA microarray was further applied in 20 HCC specimens and all available cell lines to figure out the gene expression profiles of those samples. Interestingly, the genomic DNA copy number alterations of most genes appeared not to be in generally parallel with the corresponding transcriptional expression. However, the transcriptional deregulation of a few genes, such as osteopontin (SPP1), transgelin 2 (TAGLN2) and PEG10, could be ascribed partially to their genomic aberrations, although the many alternative mechanisms could be involved in the deregulation of these genes. In general, this work would provide new insights into the genetic mechanisms in hepatocarcinogenesis associated with hepatitis B virus through the comprehensive survey on correlation between genomic DNA copy number alterations and transcriptional expression.
Huang
Jian
J
Chinese National Human Genome Center at Shanghai, 351 Guo Shou-Jing Road, Shanghai 201203, China.
Sheng
Hai-Hui
HH
Shen
Ting
T
Hu
Yuan-Jie
YJ
Xiao
Hua-Sheng
HS
Zhang
Qin
Q
Zhang
Qing-Hua
QH
Han
Ze-Guang
ZG
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D002875:Chromosomes / Q000235:genetics; D004247:DNA / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics*; D006509:Hepatitis B / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D008840:Microfilament Proteins; D009124:Muscle Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D004247:DNA