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Renal Cell Carcinoma: Molecular Aspects

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Abstract

Renal cell carcinoma is the most common form of the kidney cancer accounting for more than 85% of the cases of which clear cell renal cell carcinoma (ccRCC) is the major histological subtype. The central molecular signature for ccRCC pathogenesis is the biallelic inactivation of VHL gene due to the presence of mutations/hyper-methylation/complete gene loss, which results in the downstream HIF activation. These events lead to increased tyrosine kinase receptor signalling pathways (RAS/MEK/ERK pathway, PI3K/AKT/mTOR pathway and NF-κB pathway), which through their downstream effector proteins causes the cell to proliferate and migrate. Recent studies have shown that VHL inactivation alone is not sufficient to induce the tumor. Mutations in numerous other genes that codes for chromatin modifiers (PBRM1, SETD2 and BAP1) and signalling proteins (PTEN and mTOR) have been identified along with activation of alternate signalling pathways like STAT and Sonic Hedgehog (SHH) pathway. It has also been shown that STAT pathway also works cooperatively with HIF to enhance the tumor progression. However, SHH pathway reactivation resulted in tumor regardless of the VHL status, indicating the complex nature of the tumor at the molecular level. Therefore, understanding the complete aetiology of ccRCC is important for future therapeutics.

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  1. Department of Biochemistry, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, India

    Aman Kumar, Niti Kumari, Vinny Gupta & Rajendra Prasad

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Kumar, A., Kumari, N., Gupta, V. et al. Renal Cell Carcinoma: Molecular Aspects. Ind J Clin Biochem 33, 246–254 (2018). https://doi.org/10.1007/s12291-017-0713-y

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