title: Epigenetic alterations of chromosome 3 revealed by NotI-microarrays in clear cell renal cell carcinoma.
abstract: 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 (P = 0.03). The same was observed for FGD5 gene in ccRCC (P < 0.06). Dedicated to thememory of Eugene R. Zabarovsky.
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia ; P.A. Herzen Moscow Oncology Research Institute, Ministry of Healthcare of the Russian Federation, Moscow 125284, Russia.
authors: Alexey A
authors: AA
authors: Dmitriev
authors: Institute of Molecular Biology and Genetics, Ukrainian Academy of Sciences, Kiev 03680, Ukraine.
authors: Evgeniya E
authors: EE
authors: Rudenko
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia ; P.A. Herzen Moscow Oncology Research Institute, Ministry of Healthcare of the Russian Federation, Moscow 125284, Russia.
authors: Anna V
authors: AV
authors: Kudryavtseva
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia ; Mechnikov Research Institute for Vaccines and Sera, Russian Academy of Medical Sciences, Moscow 105064, Russia.
authors: George S
authors: GS
authors: Krasnov
authors: Institute of Molecular Biology and Genetics, Ukrainian Academy of Sciences, Kiev 03680, Ukraine.
authors: Vasily V
authors: VV
authors: Gordiyuk
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
authors: Nataliya V
authors: NV
authors: Melnikova
authors: National Cancer Institute, Kiev 03022, Ukraine.
authors: Eduard O
authors: EO
authors: Stakhovsky
authors: National Cancer Institute, Kiev 03022, Ukraine.
authors: Oleksii A
authors: OA
authors: Kononenko
authors: N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow 115478, Russia.
authors: Larissa S
authors: LS
authors: Pavlova
authors: N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow 115478, Russia.
authors: Tatiana T
authors: TT
authors: Kondratieva
authors: P.A. Herzen Moscow Oncology Research Institute, Ministry of Healthcare of the Russian Federation, Moscow 125284, Russia.
authors: Boris Y
authors: BY
authors: Alekseev
authors: Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russia ; Research Center of Medical Genetics, Russian Academy of Medical Sciences, Moscow 115478, Russia.
authors: Eleonora A
authors: EA
authors: Braga
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
authors: Vera N
authors: VN
authors: Senchenko
authors: Institute of Molecular Biology and Genetics, Ukrainian Academy of Sciences, Kiev 03680, Ukraine ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.
authors: Vladimir I
authors: VI
authors: Kashuba
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*
chemical_list: D005819:Genetic Markers; D009363:Neoplasm Proteins