The epigenetic landscape of renal cancer

Abstract

| The majority of kidney cancers are associated with mutations in the von Hippel-Lindau gene and a small proportion are associated with infrequent mutations in other well characterized tumour-suppressor genes. In the past 15 years, efforts to uncover other key genes involved in renal cancer have identified many genes that are dysregulated or silenced via epigenetic mechanisms, mainly through methylation of promoter CpG islands or dysregulation of specific microRNAs. In addition, the advent of next-generation sequencing has led to the identification of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and SETD2, which are all involved in histone modification and nucleosome and chromatin remodelling. In this Review, we discuss how altered DNA methylation, microRNA dysregulation and mutations in histone-modifying enzymes disrupt cellular pathways in renal cancers.

Di-Ras2 Promotes Renal Cell Carcinoma Formation by Activating the MAPK Pathway in the Absence of VHL

“…Early diagnosis of the disease is difficult, and metastases often occur before the primary tumor is detected. Therefore, radical nephrectomy is considered to be the most effective way to treat ccRCC [9, 10]. But the five-year survival rate for individuals with metastatic disease is still less than 10% [11].…”

“…But the five-year survival rate for individuals with metastatic disease is still less than 10% [11]. It has been reported that hepatocyte growth factor (HGF) binding to its receptor, tyrosine-protein kinase Met, leads to activation of the Ras/MAPK signaling pathway to promote ccRCC growth and metastasis [9, 12]. Function of the RAS-Mitogen activated protein kinase (MAPK) signaling pathway (also known as the RAS-RAF-MEK-ERK pathway) is to integrate extracellular signals and to coordinate a suitable response by a subsequent control of cellular growth, survival, and differentiation[13].…”

Association of E‐cadherin methylation with risk of nasopharyngeal cancer: A meta‐analysis

“…It leads to gene silencing and contributing to carcinogenesis and development of cancers . Thus, detection of aberrant gene promoter methylation in biopsy specimens and noninvasive body fluids, like serum, has been widely used for diagnosis of different tumors, such as lung cancer, breast cancer, gastric cancer, renal cancer, and NPC . As a nonnegligible gene related to initiation and invasion of cancers, aberrant methylation of the E‐cadherin gene, which leads to E‐cadherin silencing, is also detected in NPC…”

Prognostic DNA Methylation Markers for Renal Cell Carcinoma: A Systematic Review

“…This is illustrated by the relative high frequency of promoter methylation as compared to the number of somatic alterations in RCC [14]. Furthermore, in contrast to somatic mutations in RCC, DNA methylation alterations are often shown to be associated with clinicopathological features and patient survival [14,15]. DNA methylation consists of the covalent addition of a methyl group to cytosines that precede a guanosine, the CpG dinucleotide, which are mainly clustered as CpG islands in the promoter region of genes [13].…”