Abstract
Hepatocellular carcinoma (HCC) is the most frequent tumour derived from the malignant transformation of hepatocytes. It is well established that cancer is a disease of the genome and, as in other types of solid tumours, a large number of genetic and epigenetic alterations are accumulated during the hepatocarcinogenesis process. Recent developments using comprehensive genomic tools have enabled the identification of the molecular diversity in human HCC. Consequently, several molecular classifications have been described using different approaches and important progress has been made particularly with the transcriptomic, genetic, chromosomal, miRNA and methylation profiling. On the whole, all these molecular classifications are related and one of the major determinants of the identified subgroups of tumours are gene mutations found in oncogenes and tumour suppressors. However, the full understanding of the HCC molecular classification requires additional comprehensive studies using both genomic and pathway analyses. Finally, a refinement of the molecular classification of HCC, taking into account the geographical and genetic diversity of the patients, will be essential for an efficient design of the forthcoming personalized clinical treatments.
Highlights
Despite our growing comprehension of the different pathways altered in hepatocellular tumors, the molecular mechanisms that lead hepatocytes to undergo transformation and give rise to a hepatocellular carcinoma are still poorly understood
Some of the observed genetic alterations are widely shared among the different tumor types; for example, mutations in CTNNB1 and TP53 genes are found in tumors developed in several different organs, as shown in the cosmic mutation database[3]
Recent analysis of large number of genetic and epigenetic alterations together with transcriptome and systematic pathway analyses enabled to clarify the diversity of Hepatocellular carcinoma (HCC) and HCA, their molecular classification and the identification of subgroups of tumors likely to be efficiently targeted by specific drugs
Summary
Both benign and malignant hepatocellular tumors demonstrate a broad diversity at the genetic and epigenetic levels leading to robust classification closely related to clinical features and carcinogenesis pathways. These molecular classifications are closely related together. Tumor suppressor and oncogene mutations are frequently major drivers of the subclasses. Classifying tumors in homogeneous sub-groups using gene signature is a promising tool to construct rational protocols with targeted therapies and to refine prognosis
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