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The role of epigenetics in kidney malignancies.

la Rosa AH, Acker M, Swain S, Manoharan M - Cent European J Urol (2015)

Bottom Line: Epigenetics can be defined as inherited modifications in gene expression that are not encoded in the DNA sequence itself.During the last decade, many different types of epigenetic alterations of DNA have been found to be associated with malignant renal tumors.This has led to the research of the diagnostic and prognostic implications of these changes in renal malignancies as well as to the development of novel drugs to target these changes, with the aim of achieving a survival benefit.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA.

ABSTRACT

Introduction: Renal cell carcinomas (RCC) are collectively the third most common type of genitourinary neoplasms, surpassed only by prostate and bladder cancer. Cure rates for renal cell carcinoma are related to tumor grade and stage; therefore, diagnostic methods for early detection and new therapeutic modalities are of paramount importance. Epigenetics can be defined as inherited modifications in gene expression that are not encoded in the DNA sequence itself. Epigenetics may play an important role in the pursuit of early diagnosis, accurate prognostication and identification of new therapeutic targets.

Material and methods: We used PubMed to conduct a comprehensive search of the English medical literature using search terms including epigenetics, DNA methylation, histone modification, microRNA regulation (miRNA) and RCC. In this review, we discuss the potential application of epigenetics in the diagnosis, prognosis and treatment of kidney cancer.

Results: During the last decade, many different types of epigenetic alterations of DNA have been found to be associated with malignant renal tumors. This has led to the research of the diagnostic and prognostic implications of these changes in renal malignancies as well as to the development of novel drugs to target these changes, with the aim of achieving a survival benefit.

Conclusions: Epigenetics has become a promising field in cancer research. The potential to achieve early detection and accurate prognostication in kidney cancer might be feasible through the application of epigenetics. The possibility to reverse these epigenetic changes with new therapeutic agents motivates researchers to continue pursuing better treatment options for kidney cancer and other malignancies.

No MeSH data available.


Related in: MedlinePlus

Epigenetic hypermethylation of CpG islands carried out by DNA methyl-transferase. A) Transcription factor attachment to DNA strand induces RNA polymerase to initiate transcription and gene expression. B) Methylation of CpG island prevents transcription factor attachment and subsequent DNA transcription and gene expression.
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Figure 0001: Epigenetic hypermethylation of CpG islands carried out by DNA methyl-transferase. A) Transcription factor attachment to DNA strand induces RNA polymerase to initiate transcription and gene expression. B) Methylation of CpG island prevents transcription factor attachment and subsequent DNA transcription and gene expression.

Mentions: Hypermethylation inactivates transcription of CpG dinucleotides in promoter regions of tumor suppressor genes leading to gene silencing [12]. Earlier studies have shown that aberrant DNA hypermethylation is involved in the pathogenesis of RCC. One study demonstrated a 100% correlation between DNA hypermethylation of the promoter gene RASSF1A and papillary RCC (pRCC) [13]. The important role of promoter hypermethylation with subsequent transcriptional silencing of tumor suppressor genes in the development of RCC was noted by Ricketts et al. In their report, they found that in patients with clear cell RCC (ccRCC), the von Hippel-Lindau (VHL) tumor suppressor gene is inactivated by promoter hypermethylation in 15% of cases [14]. Several enzymes called DNA methyltransferases (DNMT) are required to accomplish the process of hypermethylation [15] (Figure 1). Hypermethylation may be analyzed by using the sensitive methylation-specific PCR (MSP) technique, which allows for the identification of a single methylated allele among hundreds of unmethylated alleles. MSP-based detection of hypermethylation has been successfully used when obtaining samples from body fluids that surround or drain the organ of interest in patients with solid malignancies [16].


The role of epigenetics in kidney malignancies.

la Rosa AH, Acker M, Swain S, Manoharan M - Cent European J Urol (2015)

Epigenetic hypermethylation of CpG islands carried out by DNA methyl-transferase. A) Transcription factor attachment to DNA strand induces RNA polymerase to initiate transcription and gene expression. B) Methylation of CpG island prevents transcription factor attachment and subsequent DNA transcription and gene expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526599&req=5

Figure 0001: Epigenetic hypermethylation of CpG islands carried out by DNA methyl-transferase. A) Transcription factor attachment to DNA strand induces RNA polymerase to initiate transcription and gene expression. B) Methylation of CpG island prevents transcription factor attachment and subsequent DNA transcription and gene expression.
Mentions: Hypermethylation inactivates transcription of CpG dinucleotides in promoter regions of tumor suppressor genes leading to gene silencing [12]. Earlier studies have shown that aberrant DNA hypermethylation is involved in the pathogenesis of RCC. One study demonstrated a 100% correlation between DNA hypermethylation of the promoter gene RASSF1A and papillary RCC (pRCC) [13]. The important role of promoter hypermethylation with subsequent transcriptional silencing of tumor suppressor genes in the development of RCC was noted by Ricketts et al. In their report, they found that in patients with clear cell RCC (ccRCC), the von Hippel-Lindau (VHL) tumor suppressor gene is inactivated by promoter hypermethylation in 15% of cases [14]. Several enzymes called DNA methyltransferases (DNMT) are required to accomplish the process of hypermethylation [15] (Figure 1). Hypermethylation may be analyzed by using the sensitive methylation-specific PCR (MSP) technique, which allows for the identification of a single methylated allele among hundreds of unmethylated alleles. MSP-based detection of hypermethylation has been successfully used when obtaining samples from body fluids that surround or drain the organ of interest in patients with solid malignancies [16].

Bottom Line: Epigenetics can be defined as inherited modifications in gene expression that are not encoded in the DNA sequence itself.During the last decade, many different types of epigenetic alterations of DNA have been found to be associated with malignant renal tumors.This has led to the research of the diagnostic and prognostic implications of these changes in renal malignancies as well as to the development of novel drugs to target these changes, with the aim of achieving a survival benefit.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA.

ABSTRACT

Introduction: Renal cell carcinomas (RCC) are collectively the third most common type of genitourinary neoplasms, surpassed only by prostate and bladder cancer. Cure rates for renal cell carcinoma are related to tumor grade and stage; therefore, diagnostic methods for early detection and new therapeutic modalities are of paramount importance. Epigenetics can be defined as inherited modifications in gene expression that are not encoded in the DNA sequence itself. Epigenetics may play an important role in the pursuit of early diagnosis, accurate prognostication and identification of new therapeutic targets.

Material and methods: We used PubMed to conduct a comprehensive search of the English medical literature using search terms including epigenetics, DNA methylation, histone modification, microRNA regulation (miRNA) and RCC. In this review, we discuss the potential application of epigenetics in the diagnosis, prognosis and treatment of kidney cancer.

Results: During the last decade, many different types of epigenetic alterations of DNA have been found to be associated with malignant renal tumors. This has led to the research of the diagnostic and prognostic implications of these changes in renal malignancies as well as to the development of novel drugs to target these changes, with the aim of achieving a survival benefit.

Conclusions: Epigenetics has become a promising field in cancer research. The potential to achieve early detection and accurate prognostication in kidney cancer might be feasible through the application of epigenetics. The possibility to reverse these epigenetic changes with new therapeutic agents motivates researchers to continue pursuing better treatment options for kidney cancer and other malignancies.

No MeSH data available.


Related in: MedlinePlus