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Genomic and Epigenomic Aberrations in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 2012

Special Issue Editor


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Guest Editor
Faculty of Health Sciences, University of Macau, Taipa, Macao
Interests: epigenomic aberrations; genomic aberrations; ntertumoral heterogeneity; HCC

Special Issue Information

Dear Colleagues,

Cancer is driven by a complex interplay of genetic and epigenetic alterations that disrupt normal cellular processes. Genomic alterations, such as somatic mutations and copy number alterations, together with epigenomic alterations, such as DNA methylation and chromatin modifications, collectively shape tumor phenotypes. Deciphering the functional impact of these alterations and the underlying mechanisms is critical for developing precision medicine strategies and improving patient outcomes.

This Special Issue aims to provide a comprehensive platform for cutting-edge research and reviews on the role of genomic and epigenomic aberrations in cancer biology. We welcome contributions that explore the spectrum of alterations across cancer subtypes, their association with recurrence, and their functional implications in processes such as metastasis, immune evasion, and metabolic rewiring. 

Submissions may include, but are not limited to the following: (1) (Epi)genomic Alterations and Cancer Subtypes: Genomic and epigenomic signatures linked to tumor classification, initiation, progression, recurrence, tumor evolution models and drug response; (2) Functional (Epi)genomics: Mechanistic insights into how alterations shape various tumor phenotypes, such as metastasis, immune escape, and metabolic reprogramming; (3) Molecular Mechanisms: Molecular pathways and regulatory potentials connecting genomic and epigenomic changes to oncogenesis and therapy resistance.

Dr. Xiaofan Ding
Guest Editor

Manuscript Submission Information

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Keywords

  • genomic mutation
  • epigenetic alteration
  • functional genomics

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Published Papers (2 papers)

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Research

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21 pages, 9015 KB  
Article
Genome-Scale CRISPR Screens Reveal DNA Repair Dependencies That Sensitize Hepatocellular Carcinoma to Oxaliplatin
by Hanyue Ouyang, Diyun Huang, Dongsheng Wen, Lichang Huang, Zichao Wu, Zhicheng Lai, Minke He, Wenchao Wu and Ming Shi
Cancers 2026, 18(9), 1360; https://doi.org/10.3390/cancers18091360 - 24 Apr 2026
Viewed by 537
Abstract
Background: Most patients with hepatocellular carcinoma (HCC) present with advanced disease and have limited systemic treatment options. Oxaliplatin shows clinical activity in HCC but its effectiveness is frequently curtailed by intrinsic and acquired resistance. We sought to systematically identify genetic vulnerabilities that [...] Read more.
Background: Most patients with hepatocellular carcinoma (HCC) present with advanced disease and have limited systemic treatment options. Oxaliplatin shows clinical activity in HCC but its effectiveness is frequently curtailed by intrinsic and acquired resistance. We sought to systematically identify genetic vulnerabilities that increase oxaliplatin sensitivity in HCC. Methods: Genome-scale negative-selection CRISPR–Cas9 screens were conducted in two genetically distinct HCC cell lines (Hep3B and MHCC-97H) under low-dose oxaliplatin to discover conserved determinants of sensitivity. Selected DNA damage response (DDR) hits were validated. An oxaliplatin-resistant MHCC-97H subline was generated for transcriptomic profiling to characterize resistance-associated programs. Screen results were integrated with TCGA-LIHC expression and survival data to evaluate clinical relevance. Additionally, we analyzed bulk RNA-seq data from biopsy specimens collected from 36 HCC patients prior to initiation of hepatic arterial infusion chemotherapy (HAIC), comparing expression levels of the DDR genes between patients with objective response and non-responders. Results: Screens in both cell lines converged on DDR pathways, particularly nucleotide excision repair (NER) and the Fanconi anemia/interstrand crosslink repair network; shared sensitizers included ERCC4 (XPF), FANCE and SLX4. Validation experiments showed that disruption of representative DDR factors (POLH and XPA) synergistically increased oxaliplatin efficacy at concentrations as low as 0.5 μM. Transcriptomic analysis of the resistant MHCC-97H subline revealed coordinated upregulation of DNA repair programs, G2/M checkpoint and E2F target signatures, and epithelial–mesenchymal transition features. Integration with TCGA-LIHC data demonstrated frequent overexpression of many screen-identified DDR genes in primary HCC and an association between higher expression of selected factors and poorer patient survival. In the HAIC cohort, several DDR genes, including ATR, BRCA2, CDK7, MUS81, MUTYH, PARG, POLH, POLK and XPA, were significantly lower in the objective response group. Conclusions: DDR components represent candidate biomarkers and therapeutic targets whose inhibition may enhance oxaliplatin efficacy in HCC. Full article
(This article belongs to the Special Issue Genomic and Epigenomic Aberrations in Cancer)
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Review

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42 pages, 1858 KB  
Review
Crosstalk Between Cis-Regulatory Elements and Metabolism Reprogramming in Hepatocellular Carcinoma
by Yuqing Ren, Di Tang, Xiaofan Ding and Mian He
Cancers 2026, 18(6), 1002; https://doi.org/10.3390/cancers18061002 - 19 Mar 2026
Viewed by 1169
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, arising from profound metabolic reprogramming and widespread epigenetic dysregulation. However, the role of epigenetic aberrations in modulating metabolic reprogramming and the interplay between cis-regulatory elements (CREs), such as promoters, enhancers and [...] Read more.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, arising from profound metabolic reprogramming and widespread epigenetic dysregulation. However, the role of epigenetic aberrations in modulating metabolic reprogramming and the interplay between cis-regulatory elements (CREs), such as promoters, enhancers and super-enhancers, and metabolic adaptation have not been systematically summarized. Therefore, this review aims to integrate current evidence to elucidate the mechanisms of how cis-regulatory elements (CREs) drive oncogenic and metabolic signals in HCC progression. For instance, enhancers and super-enhancers transcriptionally activate key metabolic genes involved in aerobic glycolysis (GLUT1, HK2, PKM2, LDHA), de novo lipogenesis (ACLY, FASN, ACC), glutaminolysis (SLC1A5, GLS), and nucleotide synthesis. Meanwhile, many metabolic intermediates, including acetyl-CoA, succinyl-CoA and lactate, act as cofactors or substrates for epigenetic modifiers, creating bidirectional feedback loops that reinforce CRE-driven malignant phenotypes. Therefore, aberrant CREs acts as “metabolic switches” that sense and respond to various metabolic conditions to sustain HCC growth. Consequently, targeted intervention against oncogenic CREs, such as super-enhancers or their co-activators, to disrupt CRE-mediated metabolic vulnerabilities, has emerged as a highly promising new paradigm for precision therapy in HCC. Full article
(This article belongs to the Special Issue Genomic and Epigenomic Aberrations in Cancer)
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