Cancer Genetics and Epigenetics 2024, Vol.12, No.3, 125-136 http://medscipublisher.com/index.php/cge 127 3.2 Significant genetic variants identified Several significant genetic variants have been identified through GWAS in liver cancer. Key driver genes and mutations frequently observed include those in the Wnt/β-catenin pathway, TP53/cell-cycle pathways, telomere maintenance, and chromatin regulators. Additionally, HBV integration into cancer-related genes is a notable driver event in hepatocarcinogenesis (Nakagawa et al., 2019). These genetic alterations are not limited to point mutations but also include structural variants, copy-number alterations, and virus integrations. The identification of these variants has provided valuable insights into the molecular mechanisms of liver cancer and has highlighted potential targets for precision medicine. For instance, actionable mutations have been identified that could guide the use of multi-kinase inhibitors and other targeted therapies, although the availability of molecular target therapies remains limited. 3.3 Epigenetic factors and their role Epigenetic factors play a crucial role in the development and progression of liver cancer. DNA methylation profiles, for example, have been used to classify liver cancer subtypes and are associated with patient prognosis. Epigenetic modifications can influence gene expression without altering the DNA sequence, thereby contributing to cancer development. These modifications include DNA methylation, histone modification, and non-coding RNA regulation. The integration of epigenetic data with GWAS findings can provide a more comprehensive understanding of liver cancer biology and identify novel therapeutic targets(Figure 1). Moreover, the study of epigenetic changes in liver cancer can help in the development of biomarkers for early detection and personalized treatment strategies (Malone et al., 2019). In summary, GWAS has significantly advanced our understanding of the genetic and epigenetic landscape of liver cancer. The identification of key genetic variants and the role of epigenetic factors offer promising avenues for the development of precision treatments tailored to individual genetic profiles. Continued research in this area is essential for translating these findings into clinical practice and improving outcomes for liver cancer patients. Figure 1 Molecular profiling for precision cancer therapies (Adopted from Malone et al., 2019) Image caption: The process from genetic sequencing of patients to enrollment on genotype-matched clinical trials. MTB, molecular tumor board; IRB, institutional review board; NGS, next-generation sequencing (Adopted from Malone et al., 2019) Malone et al. (2019) found that the process from molecular profiling to genotype-drug matching in clinical trials faces numerous challenges, leading to significant patient attrition. These challenges span various stages, including patient accrual, sample collection, laboratory operations, variant interpretation, clinical utility, decision-making, clinical interpretation, and trial matching. Specific issues include patient-related factors, inadequate sample collection, technical issues with next-generation sequencing (NGS), difficulties in variant interpretation, low rates of actionable results, lack of access to molecular tumor boards (MTBs), and insufficient access to drugs or clinical trials. Possible solutions proposed by the authors include better patient selection, improved sample processing,
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