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Published on: January 22, 2013
An Overview of Epigenetics in Clear Cell Renal Cell Carcinoma
Stamatiki Grammatikaki1, Hector Katifelis1, Ammad Ahmad Farooqi2
1Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Abstract:
Renal cell carcinoma (RCC) represents a heterogenous group of cancers with complex genetic background and histological varieties, which require various clinical therapies. Clear cell RCC represents the most common form of RCC that accounts for 3 out of 4 RCC cases. Screening methods for RCC lack sensitivity and specificity, and thus biomarkers that will allow early diagnosis are crucial. The impact of epigenetics in the development and progression of cancer, including RCC, is significant. Noncoding RNAs, histone modifications and DNA methylation represent fundamental epigenetic mechanisms and have been proved to be promising biomarkers. MicroRNAs have advantageous properties that facilitate early diagnosis of RCC, while their expression profiles have been assessed in renal cancer samples (tissue, blood, and urine). Current literature reports the up-regulation of mir122, mir1271 and mir15b in RCC specimens, which induces cell proliferation via FOXP-1 and PTEN genes. However, it should be noted that conflicting results are found in urine and serum patient samples. Moreover, promoters of at least 200 genes are methylated in renal cancers leading to epigenetic dysregulation. In this review, we analyze the vast plethora of studies that have evaluated the role of epigenetic mechanisms in RCC patients and their clinical importance.
Insights
Epigenetic mechanisms like DNA methylation and microRNAs are crucial for early renal cell carcinoma (RCC) diagnosis. These biomarkers show promise for identifying RCC, despite some conflicting results in patient samples.
Area of Science:
- Oncology
- Epigenetics
- Biomarker Discovery
Background:
- Renal cell carcinoma (RCC) is a heterogeneous cancer with complex genetics.
- Clear cell RCC is the most common subtype, accounting for 75% of cases.
- Current screening methods for RCC lack sensitivity and specificity, necessitating early diagnostic biomarkers.
Purpose of the Study:
- To review the role of epigenetic mechanisms in renal cell carcinoma (RCC) development and progression.
- To highlight the potential of epigenetic modifications as biomarkers for early RCC diagnosis.
- To analyze the clinical importance of epigenetic alterations in RCC patients.
Main Methods:
- Literature review of studies evaluating epigenetic mechanisms in RCC.
- Analysis of noncoding RNAs (microRNAs), histone modifications, and DNA methylation in RCC.
- Assessment of microRNA expression profiles in various RCC patient samples (tissue, blood, urine).
Main Results:
- Epigenetic mechanisms, including noncoding RNAs, histone modifications, and DNA methylation, are significantly implicated in RCC.
- MicroRNAs (e.g., mir122, mir1271, mir15b) show altered expression in RCC, potentially affecting cell proliferation via genes like FOXP-1 and PTEN.
- DNA methylation affects promoters of over 200 genes in renal cancers, leading to epigenetic dysregulation, though some findings vary between sample types.
Conclusions:
- Epigenetic alterations represent promising avenues for early RCC detection and diagnosis.
- MicroRNAs and DNA methylation patterns are key epigenetic factors in RCC pathogenesis.
- Further research is needed to reconcile conflicting results and establish robust epigenetic biomarkers for clinical application in RCC.
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