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Optical genome and epigenome mapping of clear cell renal cell carcinoma
S. Margalit, Z. Tulpová, Y. Michaeli, TD. Zur, J. Deek, S. Louzoun-Zada, G. Nifker, A. Grunwald, Y. Scher, L. Schütz, E. Weinhold, Y. Gnatek, D. Omer, B. Dekel, E. Friedman, Y. Ebenstein
Language English Country England, Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural
Grant support
R01 HG009190
NHGRI NIH HHS - United States
NLK
Directory of Open Access Journals
from 2020
PubMed Central
from 2019
Oxford Journals Open Access Collection
from 2019-12-01
ROAD: Directory of Open Access Scholarly Resources
from 2019
- MeSH
- DNA-Binding Proteins MeSH
- Epigenesis, Genetic * genetics MeSH
- Epigenome * genetics MeSH
- Carcinoma, Renal Cell * genetics pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Chromosome Mapping methods MeSH
- DNA Methylation * genetics MeSH
- Von Hippel-Lindau Tumor Suppressor Protein genetics MeSH
- Kidney Neoplasms * genetics pathology MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Transcription Factors MeSH
- DNA Copy Number Variations * genetics MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Cancer cells display complex genomic aberrations that include large-scale genetic rearrangements and epigenetic modulation that are not easily captured by short-read sequencing. This study presents a novel approach for simultaneous profiling of long-range genetic and epigenetic changes in matched cancer samples, focusing on clear cell renal cell carcinoma (ccRCC). ccRCC is a common kidney cancer subtype frequently characterized by a 3p deletion and the inactivation of the von Hippel-Lindau (VHL) gene. We performed integrated genetic, cytogenetic, and epigenetic analyses on paired tumor and adjacent nontumorous tissue samples. Optical genome mapping identified genomic aberrations as structural and copy number variations, complementing exome-sequencing findings. Single-molecule methylome and hydroxymethylome mapping revealed a significant global reduction in 5hmC level in both sample pairs, and a correlation between both epigenetic signals and gene expression was observed. The single-molecule epigenetic analysis identified numerous differentially modified regions, some implicated in ccRCC pathogenesis, including the genes VHL, PRCC, and PBRM1. Notably, pathways related to metabolism and cancer development were significantly enriched among these differential regions. This study demonstrates the feasibility of integrating optical genome and epigenome mapping for comprehensive characterization of matched tumor and adjacent tissue, uncovering both established and novel somatic aberrations.
Department of Biomedical Engineering Tel Aviv University 6997801 Tel Aviv Israel
Institute of Experimental Botany of the Czech Academy of Sciences 77900 Olomouc Czech Republic
Institute of Organic Chemistry RWTH Aachen University D 52056 Aachen Germany
References provided by Crossref.org
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