Correlation between genomic DNA copy number alterations and transcriptional expression in hepatitis B virus‐associated hepatocellular carcinoma

Abstract

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 genomewide 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.

Identification of novel molecular targets regulated by tumor suppressive miR-1/miR-133a in maxillary sinus squamous cell carcinoma

“…The protein encoded by the TAGLN gene is an actinbinding protein like TAGLN2, found in fibroblasts and smooth muscle (32). Overexpression of TAGLN2 was observed in hepatocellular carcinoma, lung adenocarcinoma, and pancreatic cancer (33)(34)(35)(36). More recently, we also found overexpression of TAGLN2 in HNSCC and bladder cancer (14,24).…”

Categorical meta-analysis of Osteopontin as a clinical cancer marker

“…Polymorphisms in the Osteopontin gene, spp1, have recently been associated with hepatocellular carcinoma (27) and with lung cancer (17). Gene amplification of spp1 has been studied in hepatocellular, ovarian and endometrial cancers (28,29). Osteopontin is subject to alternative splicing.…”

Development of a survival prediction model for gastric cancer using serine proteases and their inhibitors

“…The cDNA microarray used in the present study consisted of 13,824 genes/ ESTs; this microarray was the same as that used by Huang et al (24) and constructed by the National Engineering Center for Biochips at Shanghai (Shanghai, China). The microarray and the experimental procedure were confirmed to be feasible by previous studies (24,25). Thus, it was used instead of a new customized microarray containing SP and serpin genes only.…”

“…A total of 30 pmol of each probe was used in the two-color array hybridization. The hybridization and scanning procedures were identical as those described previously (24).…”