DNA Methylation and Epigenetic Events Underlying Renal Cell Carcinomas

Abstract

Renal cell carcinoma (RCC) refers to a group of tumors that develop from the epithelium of the kidney tubes, including clear cell RCC, papillary RCC, and chromophobe RCC. Most clear cell renal carcinomas have a large histologic subtype, genetic or epigenetic von Hippel-Lindau (VHL). A comprehensive analysis of the genetic modification genome suggested that chromosome 3p loss and chromosome gains 5q and 7 may be significant copy defects in the development of clear RCC. A more potent RCC may develop if chromosome 1p, 4, 9, 13q, or 14q is also lost. Renal carcinogenesis is not associated with chronic inflammation or histological changes. However, if regional hypermethylation of DNA in CpG C-type islands has already accumulated in cancer-free kidney tissue, it implies that the presence of malignant kidney lesions may also be detected by modified DNA methylation. Modification of DNA methylation in cancerous kidney tissue may advance kidney tissue to epigenetic mutations and genes, leading to more serious cancers and even determining a patient's outcome. The genetic and epigenetic profile provides accurate predictors for patients with kidney cancer. New genetic and epigenetic analysis technologies will help to speed up the identification of vital cells for kidney cancer prevention, diagnosis, and treatment.

Free-fatty acid receptor-1 (FFA1/GPR40) promotes papillary RCC proliferation and tumor growth via Src/PI3K/AKT/NF-κB but suppresses migration by inhibition of EGFR, ERK1/2, STAT3 and EMT

“…In addition to chromosomal gain, loss of chromosome 9p and intra-chromosomal rearrangement of chromosomes 1–3 have also been identified in pRCC [ 62 , 64 , 65 ], and together, these alterations reflect a broad expanse towards pathological variability. In addition to genetic heterogeneity, DNA methylation and epigenetic modifications also contribute to RCC variability [ 66 ]. Chromosomal alterations have been shown to directly impact many genes in pRCC including the protooncogene MET, which is common to type 1 pRCC, as well as cyclin-dependent kinase inhibitor 2A (CDKN2A) and downstream cell-cycle related proteins, including Hippo/YAP1, p53, and mTOR.…”

Biomarkers in renal cell carcinoma and their targeted therapies: a review

“…Recently it was revealed that inhibitors of the NOTCH LY-3039478 results in an increase in survival in ccRCC xenografts, indicating an alternative treatment for RCC [ 109 ]. It was reported that several DNA methylation inhibiting drugs such as azacytidine oligonucleotide MG98 as well as drugs belonging to histone deacetylase inhibitors (HDACis) class such as vorinostat, panobinostat, romidepsin, and belinostat are in phase I/II clinical trials and are being considered for RCC targeted therapy [ 109 ].…”

“…Amongst these anti-DLL4 humanized antibodies or bispecific monoclonal antibodies targeting both human DLL4 and human VEGF such as navicixizumab (knob-in-hole), HD-105 (scFv 2 -Fc), HB-32 (CrossMAb) and ABT-165 (DVD-Ig) have been established and are under clinical trials to assess for their safety and efficacy. Besides, recombinant proteins and miRNA have also been studied to modulate the activity of DLL4 [108]. Di Martino et al [53],…”

DNA Methylation as Drug Sensitivity Marker in RCC: A Systematic Review

“…Several molecular factors involved in these pathways are potential predictive biomarkers. Epigenetic alterations, which have also been linked to renal carcinogenesis and tumor aggressiveness [ 8 ], offer a promising molecular mechanism with predictive value in the metastatic setting of RCC. Certain genes appear to influence the response to systemic agents in a methylation-dependent manner [ 9 ].…”