Carcinogenesis often involves significant alterations in the cancer genome architecture, marked by large structural and copy number variations (SVs and CNVs) that are difficult to capture with short-read sequencing. Traditionally, cytogenetic techniques are applied to detect such aberrations, but they are limited in resolution and do not cover features smaller than several hundred kilobases. Optical genome mapping and nanopore sequencing are attractive technologies that bridge this resolution gap and offer enhanced performance for cytogenetic applications. These methods profile native, individual DNA molecules, thus capturing epigenetic information. We applied both techniques to characterize a clear cell renal cell carcinoma (ccRCC) tumor's structural and copy number landscape, highlighting the relative strengths of each method in the context of variant size and average read length. Additionally, we assessed their utility for methylome and hydroxymethylome profiling, emphasizing differences in epigenetic analysis applicability.

Department of Biomedical Engineering Tel Aviv University 6997801 Tel Aviv Israel

Department of Chemistry Raymond and Beverly Sackler Faculty of Exact Sciences Tel Aviv University 6997801 Tel Aviv Israel

Institute of Experimental Botany of the Czech Academy of Sciences Olomouc Czech Republic

Pediatric Nephrology Unit The Edmond and Lily Safra Children's Hospital Sheba Medical Center 52621 Ramat Gan Israel

Pediatric Stem Cell Research Institute Edmond and Lily Safra Children's Hospital Sheba Medical Center 52621 Ramat Gan Israel

School of Medicine Faculty of Medical and Health Sciences Tel Aviv University 6997801 Tel Aviv Israel

The Genetics Institute and Genomics Center Tel Aviv Sourasky Medical Center Tel Aviv Israel

Aktualizováno

NAR Genom Bioinform. 2025 Jan 07;7(1):lqae190. doi: 10.1093/nargab/lqae190. PubMed

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