Long-read sequencing of an advanced cancer cohort resolves rearrangements, unravels haplotypes, and reveals methylation landscapes

The Long-Read Personalized OncoGenomics (POG) dataset comprises a cohort of 189 patient tumors and 41 matched normal samples sequenced using the Oxford Nanopore Technologies PromethION platform. This dataset from the POG program and the Marathon of Hope Cancer Centres Network includes DNA and RNA short-read sequence data, analytics, and clinical information. We show the potential of long-read sequencing for resolving complex cancer-related structural variants, viral integrations, and extrachromosomal circular DNA. Long-range phasing facilitates the discovery of allelically differentially methylated regions (aDMRs) and allele-specific expression, including recurrent aDMRs in the cancer genes RET and CDKN2A. Germline promoter methylation in MLH1 can be directly observed in Lynch syndrome. Promoter methylation in BRCA1 and RAD51C is a likely driver behind homologous recombination deficiency where no coding driver mutation was found. This dataset demonstrates applications for long-read sequencing in precision medicine and is available as a resource for developing analytical approaches using this technology. [Display omitted] •We present a rich data resource of 189 long-read-sequenced patient tumors•Long-range phasing confirms biallelic tumor suppressor inactivation•Complex SVs, viral integration, and ecDNA can be resolved•Data phase promoter methylation in key cancer genes with therapeutic implications We present a resource dataset of 189 long-read-sequenced tumors from advanced cancer patients. Long-read sequencing allows detection of a range of features not easily detectable with more conventional short-read sequencing, including methylation, phasing, and complex rearrangements, with potential to enhance personalized cancer medicine.