Genetics of Hepatocellular Carcinoma: From Tumor to Circulating DNA.
Claudia CampaniJessica Zucman-RossiJean-Charles NaultPublished in: Cancers (2023)
Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies and is one of the major causes of cancer-related death. Over the last 15 years, the molecular landscape of HCC has been deciphered, with the identification of the main driver genes of liver carcinogenesis that belong to six major biological pathways, such as telomere maintenance, Wnt/b-catenin, P53/cell cycle regulation, oxidative stress, epigenetic modifiers, AKT/mTOR and MAP kinase. The combination of genetic and transcriptomic data composed various HCC subclasses strongly related to risk factors, pathological features and prognosis. However, translation into clinical practice is not achieved, mainly because the most frequently mutated genes are undruggable. Moreover, the results derived from the analysis of a single tissue sample may not adequately catch the intra- and intertumor heterogeneity. The analysis of circulating tumor DNA (ctDNA) is broadly developed in other types of cancer for early diagnosis, prognosis and monitoring under systemic treatment in order to identify primary and secondary mechanisms of resistance. The aim of this review is to describe recent data about the HCC molecular landscape and to discuss how ctDNA could be used in the future for HCC detection and management.
Keyphrases
- circulating tumor
- cell proliferation
- cell cycle
- cell free
- circulating tumor cells
- single cell
- risk factors
- genome wide
- oxidative stress
- clinical practice
- electronic health record
- dna methylation
- big data
- single molecule
- stem cells
- gene expression
- rna seq
- signaling pathway
- squamous cell carcinoma
- machine learning
- dna damage
- young adults
- copy number
- deep learning
- diabetic rats
- ischemia reperfusion injury
- drug induced
- replacement therapy