Cancer Genetics and Epigenetics 2024, Vol.12, No.4, 166-181 http://medscipublisher.com/index.php/cge 170 Figure 2 Global view of DNA and RNA alterations that affect tumours (Adopted from Calabrese et al., 2020) Image caption: a, The median numbers of different alterations across histotypes. Histotypes are ordered by hierarchical clustering based on the pattern of different types of alteration. Only histotypes with more than 10 donors are shown. Alt., alternative; non-syn, non-synonymous. Cancer-type abbreviations are listed in Supplementary Table 23. b, c, Circular representations of the selected genes significantly co-occurred with B2M (b) and PCBP2 (c). Connecting lines indicate the specific types of co-occurrence of alteration pairs. The inner histograms indicate the frequencies of incidences of different alteration types shown in different colours. d, All 74 Catalogue of Somatic Mutations in Cancer (COSMIC) cancer census genes or PCAWG driver genes that are both frequently and heterogeneously altered across both RNA- and DNA-level alterations. Yellow bars indicate the proportion of samples that had DNA-level alterations, and green bars indicate the proportion of samples with RNA-level alterations. Middle column is the proportion of each alteration type observed for that gene. e, The enrichment of cancer genes within our list of significantly recurrent genes (Adopted from Calabrese et al., 2020) 4.2 Epigenetic modifications Epigenetic modifications play a crucial role in the regulation of gene expression and are pivotal in the pathogenesis of breast cancer. These modifications include DNA methylation, histone modifications, and the involvement of non-coding RNAs. DNA Methylation: DNA methylation typically occurs at CpG islands and is associated with gene silencing. Aberrant DNA methylation patterns, such as hypermethylation of tumor suppressor genes and hypomethylation of oncogenes, are common in breast cancer and contribute to tumorigenesis (Sharma et al., 2010; Baylin and Jones, 2016). For example, hypermethylation of the BRCA1 promoter is frequently observed in sporadic breast cancers, leading to reduced expression of this critical DNA repair gene (Davalos and Esteller, 2023). Histone Modifications: Histone proteins undergo various post-translational modifications, including methylation, acetylation, phosphorylation, and ubiquitination. These modifications can either activate or repress gene transcription. In breast cancer, dysregulation of histone-modifying enzymes, such as histone deacetylases (HDACs) and histone methyltransferases, has been implicated in the aberrant expression of genes involved in cell cycle regulation, apoptosis, and metastasis (Gray et al., 2022; Szczepanek et al., 2023). For instance, overexpression of HDACs can lead to the deacetylation and inactivation of tumor suppressor genes, promoting cancer progression (Szczepanek et al., 2023).
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