Functionnal genomic of solid tumors

Hepatocellular carcinoma (HCC) is a disease of the genome and each HCC is unique combination of somatic genetic alterations. Aging, exposition to genotoxic such as aflatoxin B1, chronic inflammation, oxidative stress as well as infection by chronic hepatitis B and C modified the mutational signatures observed in primary liver tumors. Moreover, hepatitis B virus has a direct oncogenic effect due to action of viral oncoprotein such as Hbx and insertion of viral DNA in human cancer genes, a phenomenon known as insertionnal mutagenesis. Recently, adeno-associated virus type 2 has been associated with occurrence of HCC on normal liver due to insertionnal mutagenesis. Moreover, genomic studies have helped to decipher the multistep process of carcinogenesis on cirrhosis with the identification of TERT (telomerase reverse transcriptase) promoter mutation as the earliest genetic alterations involved in malignant transformation. Finally, the description of the genetic landscape of HCC will help to perform clinical trials guided by the tumor biology.