SOMATIC MUTATIONS ARE THE MAIN EVENTS OF CARCINOGENESIS IN CLEAR CELL RENAL CANCER

DOI: https://doi.org/None

D.S. Mikhaylenko (1), A.V. Kolpakov (2), N.E. Kushlinskii (2) 1 -N. Lopatkin Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Center of the Ministry of Health of Russia, 3rd Parkovaya st., 51/4, Moscow, 105425, Russian Federation; 2 -N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Kashirskoe shosse, 24, Moscow, 115478, Russian Federation

Renal cancer is among the most common oncourological diseases, and represents a heterogeneous group of tumors, which up to 80% is a clear cell renal cancer (CCRC). The study of rare hereditary forms of CCRC led to identification of the VHL gene; germinal VHL mutations cause the von Hippel-Lindau syndrome, and somatic VHL mutations are often occur in sporadic CCRC. In recent years, somatic mutations in new candidate genes of sporadic CCRC were discovered with using of the next generation sequencing (NGS). Alterations in PBRM1 gene involved in chromatin remodeling is the second most common mutation in CCRC. Mutations in PBRM1 occur irrespective of VHL mutations, they are in positive correlation with mutations in SETD2 and negative – with BAP1 genes mutations. CCRC have different pathologic features and prognosis depending on the PBRM1/BAP1 mutation status. The main stages of clonal evolution of CCRC were characterized, as soon as a sufficient intratumoral genetic heterogeneity of early CCRC. However, the subclones acquire different secondary mutations during clonal evolution. These mutations lead to activation of the mTOR and VEGF signaling pathways, as well as altering the mechanisms of chromatin remodeling and TP53 function. This article includes a current data analysis focused on mutations as the main events of initiation and progression of CCRC.
Keywords: 
clear cell renal cancer, mutation, clonal evolution

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