Genetics And Epigenetics Of Liver Cancer

abstract and Introduction Hepatocellular carcinoma (HCC) represents a major form of primary liver cancer in adults. Chronic infections with hepatitis B (HBV) and C (HCV) viruses and alcohol abuse are the major factors leading to HCC. This deadly cancer affects more than ۵۰۰,۰۰۰ people worldwide and it is quite resistant to conventional chemo- and radiotherapy. Genetic and epigenetic studies on HCC may help to understand better its mechanisms and provide new tools for early diagnosis and therapy. Recent literature on whole genome analysis of HCC indicated a high number of mutated genes in addition to well-known genes such as TP۵۳, CTNNB۱, AXIN۱ and CDKN۲A, but their frequencies are much lower. Apart from CTNNB۱ mutations, most of the other mutations appear to result in loss-of-function. Thus, HCC-associated mutations cannot be easily targeted for therapy. Epigenetic aberrations that appear to occur quite frequently may serve as new targets. Global DNA hypomethylation, promoter methylation, aberrant expression of non-coding RNAs and dysregulated expression of other epigenetic regulatory genes such as EZH۲ are the best-known epigenetic abnormalities.Chronic liver injury associated primarily with hepatitis B (HBV) and C (HCV) virus infection constitutes the most important cause of HCC Methodes Liver cancer, primarily hepatocellular carcinoma (HCC), is influenced by both genetic and epigenetic factors. Understanding these mechanisms can provide insights into tumor development, progression, and treatment. Here’s a breakdown of genetic and epigenetic methods used to study liver cancer: ۱. Genetic Methods in Liver Cancer Genetic methods focus on the mutations and alterations in DNA sequences that can drive liver cancer development. Some key techniques include: A. Whole Genome Sequencing (WGS) Purpose: Detects all genetic mutations in the liver cancer genome, including single nucleotide variants (SNVs), insertions/deletions (indels), and structural variations (SVs). Application: Identifies cancer driver mutations (e.g., mutations in the TP۵۳ or CTNNB۱ genes) and other genetic alterations. B. Whole Exome Sequencing (WES) Purpose: Targets protein-coding regions (exons) of the genome to identify mutations in genes relevant to liver cancer. Application: Commonly used to discover mutations in oncogenes or tumor suppressor genes, such as TERT, TP۵۳, and AXIN۱. ۲. Epigenetic Methods in Liver Cancer Epigenetic modifications refer to heritable changes in gene expression that do not involve changes in the DNA sequence, including DNA methylation, histone modifications, and non-coding RNAs. Methods in epigenetics focus on these regulatory processes. A. DNA Methylation Analysis Purpose: Measures the addition of methyl groups to cytosine residues in CpG islands, which often leads to gene silencing. Application: Hypermethylation of tumor suppressor genes (e.g., RASSF۱A, CDKN۲A) and hypomethylation of oncogenes can drive liver cancer progression. B. Histone Modification Analysis Purpose: Studies the post-translational modifications of histone proteins, such as acetylation, methylation, and phosphorylation, which influence chromatin structure and gene expression. Application: Aberrant histone modifications (e.g., H۳K۲۷me۳, H۳K۴me۳) are linked to the dysregulation of oncogenes and tumor suppressor genes in liver cancer. Conclusion The combination of genetic and epigenetic methods provides a powerful toolset to understand liver cancer's underlying mechanisms. These methods not only help in identifying potential biomarkers for early detection but also open avenues for precision medicine, targeting specific genetic mutations or epigenetic alterations.

کلیدواژه ها:

Genetic ، Epigenesis ، Liver ، Humans