Cancer epigenetics in solid organ tumours: A primer for surgical oncologists

Abstract

Cancer is initiated through both genetic and epigenetic alterations. The end-effect of such changes to the DNA machinery is a set of uncontrolled mechanisms of cell division, invasion and, eventually, metastasis. Epigenetic changes are now increasingly appreciated as an essential driver to the cancer phenotype. The epigenetic regulation of cancer is complex and not yet fully understood, but application of epigenetics to clinical practice and in cancer research has the potential to improve cancer care. Epigenetics changes do not cause changes in the DNA base-pairs (and, hence, does not alter the genetic code per se) but rather occur through methylation of DNA, by histone modifications, and, through changes to chromatin structure to alter genetic expression. Epigenetic regulators are characterized as writers, readers or erasers by their mechanisms of action. The human epigenome is influenced from cradle to grave, with internal and external life-time exposure influencing the epigenetic marks that may act as modifiers or drivers of carcinogenesis. Preventive and public health strategies may follow from better understanding of the lifetime influence of the epigenome. Epigenetics may be used to define risk, to investigate mechanisms of carcinogenesis, to identify biomarkers, and to identify novel therapeutic options. Epigenetic alterations are found across many solid cancers and are increasingly making clinical impact to cancer management. Novel epigenetic drugs may be used for a more tailored and specific response to treatment of cancers. We present a primer on epigenetics for surgical oncologists with examples from colorectal cancer, breast cancer, pancreatic cancer and hepatocellular carcinoma.

Methylation Profile of X-Chromosome–Related Genes in Male Breast Cancer

“…Furthermore, gene methylation constitutes an attractive research focus in oncology, often useful to detect prognostic and therapeutically important cancer profiles (13). Due to its rarity, only a few studies focused on MBC methylation profiles (3).…”

Comprehensive analysis on expression profile and prognostic values of SYTs family members and their methylation in gastric cancer

“…Foschini MP et al discovered that MAGEA family members were hypomethylation in male breast cancer (MBC) leading to their overexpression, which enhanced the androgen receptor (AR) activity and AR therapy response 21 . Meanwhile, gene methylation has constituted an attractive research eld in oncology, especially useful to predict prognostic and therapeutical signi cance of cancer pro le 22 . However, no study has been published on methylation levels of SYTs family members in GC.…”

A High Epigenetic Risk Score Shapes the Non-Inflamed Tumor Microenvironment in Breast Cancer

“…Although previous studies at different omics levels, such as somatic mutations, gene expression, non-coding RNA, and copy number variations, have revealed numerous promising biomarkers relevant to BC carcinogenesis (Zhang et al, 2018a;Fan et al, 2019;He et al, 2019;Li et al, 2019a), the contribution of epigenetic alterations including DNA methylation in human disease, particularly in cancer, has also been widely recognized (Khaled and Bidet, 2019;Luo et al, 2020;Yang et al, 2020). From the point of view of mechanism, DNA methylation, as inherently reversible changes to repress the transcriptional activities and interact with various negative and positive feedback processes, plays decisive roles in both physiological and pathological regulation of cellular fate (Drake and Søreide, 2019). Accumulated evidence highlights the multifaceted DNA methylation of 5′-cytosine-phosphate-guanine-3′ (CpG) sites in various cancer hallmarks, including modulating energy metabolism and angiogenesis, sustaining proliferation signaling, epithelial-mesenchymal transition, invasiveness, and metastasis, mainly via promoting the activation of oncogenes and silencing of tumor suppressor genes (Pasculli et al, 2018;Drake and Søreide, 2019).…”

“…From the point of view of mechanism, DNA methylation, as inherently reversible changes to repress the transcriptional activities and interact with various negative and positive feedback processes, plays decisive roles in both physiological and pathological regulation of cellular fate (Drake and Søreide, 2019). Accumulated evidence highlights the multifaceted DNA methylation of 5′-cytosine-phosphate-guanine-3′ (CpG) sites in various cancer hallmarks, including modulating energy metabolism and angiogenesis, sustaining proliferation signaling, epithelial-mesenchymal transition, invasiveness, and metastasis, mainly via promoting the activation of oncogenes and silencing of tumor suppressor genes (Pasculli et al, 2018;Drake and Søreide, 2019). The tumor microenvironment, intra-tumoral cell typing, and subsequent response to immunotherapy could also be evaluated and characterized by DNA methylation profiling (Jeschke et al, 2015;Jeschke et al, 2017;Calle-Fabregat et al, 2020).…”