**10. References**

10 Liver Tumors

The recent studies have used cross-species comparative genomics approach, that identifies genes that are conserved in animal models of cancer and in human cancer, that would facilitate the identification of critical regulatory modules conserved across species in the expression profiles and to understand the molecular pathogenesis of various cancers, including HCC [36, 54, 101-103]. The cross-species comparative analysis of animal models and human HCCs

would provide new therapeutic strategies to maximize the efficiency of treatments.

**therapeutic targets and biomarker discovery** 

and survival [17].

**9. Future directions** 

**8. Integrative and comparative analyses of HCC for identification of novel** 

It has been shown that CNAs have clear impact on expression levels in a variety of tumors [9, 13, 15]. The presence of such CNAs and LOH may contribute to cancer formation [9-11]. Integrating the gene expression with the CNA data reveals the chromosomal regions with concordantly altered genomic and transcriptional status in tumors [12, 52, 104]. The pattern of genomic modifications in a tumor represents a structural fingerprint that may include the transcriptional control mechanisms and locally impact gene expression levels [10, 12]. Therefore, focusing on differentially-expressed genes with concomitant altered DNA copy number may identify novel early HCC markers of malignant transformation, progression

The studies using integrative analysis of genomic aberrations with the expression profiling demonstrated the usefulness of this approach to identify the likely drivers of cancer [105] and helped better understand the processes affected by the drivers/passenger factors and

In this context, we performed cross-species and integrative genomic analysis to identify potential biomarker genes for early HCC [54]. In this study, we first developed a rat model of early HCC as well as liver regeneration post-hepatectomy and compared them to normal liver using a microarray approach. We then performed a cross-species comparative analysis coupled with CNAs of early human HCCs to identify the critical regulatory modules conserved across species. We identified 35 gene signature conserved across species, with more than 50% mapping to human CNA regions associated with HCC [54]. Combining cross-species comparative and/or functional genomics approaches from human and animal models of HCC along with genomic DNA copy number alterations enhances the ability to

Elucidating the molecular pathogenesis of HCC on human samples has been an onerous task due to certain limitations such as varying etiologies among studied patients, changes likely to arise during the different stages of the disease or progression of HCC, and heterogeneity of the disease. Moreover, the success of studies is hampered by the fact that hepatic transcriptome is among the most complex of any organ, and the study of tumor formation in liver can be thorny and complicated by the continuous change of the transcriptome during liver regeneration after hepatectomy. Besides, cancer progresses through a series of histopathological stages during which genetic alterations accumulate

led to obtain novel insights into pathobiology of HCC [17, 54, 105].

identify robust predictive markers for HCC [13, 36, 52-54].


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