Optical Genome and Epigenome Mapping of Clear Cell Renal Cell Carcinoma

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 non-tumorous 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.

Optical genome and epigenome mapping data of a ccRCC tumor and a normal adjacent tissue from two patients. 

Files include:

Optical Genome Mapping (OGM) files:

Bionano Genomics .bnx (molecules) files and assembly results:

Genetics_advanced_stage_ccRCC_tumor_molecules.bnx.gz

Genetics_early_stage_ccRCC_adjacent_molecules.bnx.gz

Genetics_early_stage_ccRCC_tumor_molecules.bnx.gz

Genetics_advanced_stage_ccRCC_adjacent_molecules.bnx.gz

Genetics_advanced_ccRCC_adjacent_DeNovoAssembly.zip

Genetics_early_ccRCC_adjacent_DeNovoAssembly.zip

Genetics_advanced_ccRCC_tumor_DeNovoAssembly.zip

Genetics_early_ccRCC_tumor_DeNovoAssembly.zip

2. Optical Epigenome Mapping (OEM):

 Bionano Genomics alignment files (.xmap, _q.cmap, _r.cmap) of 5hmC and unmethylation (reduced representation optical methylation mapping - ROM, with MtaqI) experiments, and processed epigenetic signal bedgraph files, of an early state ccRCC tumor and normal adjacent tissue:

OEM_early_stage.rar

Similar data, obtained from an advanced stage ccRCC sample, can be found in: 10.5281/zenodo.14266624