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BioMed Research International
Volume 2014, Article ID 735292, 9 pages
Research Article

Epigenetic Alterations of Chromosome 3 Revealed by NotI-Microarrays in Clear Cell Renal Cell Carcinoma

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
2P.A. Herzen Moscow Oncology Research Institute, Ministry of Healthcare of the Russian Federation, Moscow 125284, Russia
3Institute of Molecular Biology and Genetics, Ukrainian Academy of Sciences, Kiev 03680, Ukraine
4Mechnikov Research Institute for Vaccines and Sera, Russian Academy of Medical Sciences, Moscow 105064, Russia
5National Cancer Institute, Kiev 03022, Ukraine
6N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow 115478, Russia
7Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russia
8Research Center of Medical Genetics, Russian Academy of Medical Sciences, Moscow 115478, Russia
9Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden

Received 19 February 2014; Revised 10 April 2014; Accepted 17 April 2014; Published 22 May 2014

Academic Editor: Carole Sourbier

Copyright © 2014 Alexey A. Dmitriev et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


This study aimed to clarify epigenetic and genetic alterations that occur during renal carcinogenesis. The original method includes chromosome 3 specific NotI-microarrays containing 180 NotI-clones associated with 188 genes for hybridization with 23 paired normal/tumor DNA samples of primary clear cell renal cell carcinomas (ccRCC). Twenty-two genes showed methylation and/or deletion in 17–57% of tumors. These genes include tumor suppressors or candidates (VHL, CTDSPL, LRRC3B, ALDH1L1, and EPHB1) and genes that were not previously considered as cancer-associated (e.g., LRRN1, GORASP1, FGD5, and PLCL2). Bisulfite sequencing analysis confirmed methylation as a frequent event in ccRCC. A set of six markers (NKIRAS1/RPL15, LRRN1, LRRC3B, CTDSPL, GORASP1/TTC21A, and VHL) was suggested for ccRCC detection in renal biopsies. The mRNA level decrease was shown for 6 NotI-associated genes in ccRCC using quantitative PCR: LRRN1, GORASP1, FOXP1, FGD5, PLCL2, and ALDH1L1. The majority of examined genes showed distinct expression profiles in ccRCC and papillary RCC. The strongest extent and frequency of downregulation were shown for ALDH1L1 gene both in ccRCC and papillary RCC. Moreover, the extent of ALDH1L1 mRNA level decrease was more pronounced in both histological types of RCC stage III compared with stages I and II (). The same was observed for FGD5 gene in ccRCC ().