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.
Authors
- James Hopkins (ORCID: https://orcid.org/0000-0003-3552-2629)
- Glenn Chang (ORCID: https://orcid.org/0000-0003-4008-1725)
- Pawan Pandoh (ORCID: https://orcid.org/0000-0001-6374-235X)
- Luis F. Paulin (ORCID: https://orcid.org/0000-0003-2567-3773)
- Richard Corbett
- Erin Pleasance (ORCID: https://orcid.org/0000-0002-5104-042X)
- Tina Wong
- Connor Frey (ORCID: https://orcid.org/0000-0002-4080-3030)
- Kasmintan A. Schrader (ORCID: https://orcid.org/0000-0002-7413-4314)
- Signe MacLennan (ORCID: https://orcid.org/0009-0000-0021-375X)
- Eleanor Lewis
- Kieran O’Neill (ORCID: https://orcid.org/0000-0001-7609-5905)
- Jessica Nelson (ORCID: https://orcid.org/0000-0002-6062-6051)
- Reanne Bowlby
- Fritz Joachim Sedlazeck (ORCID: https://orcid.org/0000-0001-6040-2691)
- Vahid Akbari (ORCID: https://orcid.org/0000-0002-9621-8180)
- Katherine Dixon (ORCID: https://orcid.org/0000-0002-7334-888X)
- Stephen Yip (ORCID: https://orcid.org/0000-0002-8514-9861)
- Cameron J. Grisdale (ORCID: https://orcid.org/0000-0003-1923-6972)
- Melissa K. McConechy (ORCID: https://orcid.org/0000-0002-1965-1095)
- Andrew J. Mungall (ORCID: https://orcid.org/0000-0002-0905-2742)
- Veronika Csizmók
- Robin Coope (ORCID: https://orcid.org/0000-0002-4685-3506)
- Dean Cheng
- Vanessa Porter (ORCID: https://orcid.org/0000-0002-7167-4884)
- Duane E. Smailus (ORCID: https://orcid.org/0000-0002-7526-3409)
- Marco A. Marra (ORCID: https://orcid.org/0000-0001-7146-7175)
- John H. Dupuis (ORCID: https://orcid.org/0000-0003-0780-9454)
- Luka Culibrk (ORCID: https://orcid.org/0000-0003-1208-1920)
- Janessa Laskin (ORCID: https://orcid.org/0000-0002-0161-9329)
- Steven J.M. Jones (ORCID: https://orcid.org/0000-0003-3394-2208)
- Richard A. Moore (ORCID: https://orcid.org/0000-0002-3572-0572)
- Karen Mungall (ORCID: https://orcid.org/0000-0002-9092-4391)
- Yaoqing Shen (ORCID: https://orcid.org/0000-0002-7978-0008)
- Laura M. Williamson (ORCID: https://orcid.org/0000-0001-7353-6533)
- Eric Chuah
- Jeremy Fan
- Andrew Galbraith (ORCID: https://orcid.org/0009-0001-1345-8833)
Institutions
- University of British Columbia (CA)
- Baylor College of Medicine (US)
- Canada's Michael Smith Genome Sciences Centre (CA)
Publication Details
- Journal
- Cell Genomics
- Published
- 2024-10-14
- DOI
- https://doi.org/10.1016/j.xgen.2024.100674
- Citations
- 26
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 6.08
Funders
- Genome Canada
- Canada Foundation for Innovation
- Genome British Columbia
- Terry Fox Foundation
- Terry Fox Research Institute
- BC Cancer Foundation
- National Institutes of Health
- Canadian Institutes of Health Research
- Canadian Cancer Society Research Institute
- British Columbia Knowledge Development Fund