EACR 2024
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Oxford Nanopore are sponsoring, exhibiting and presenting at this event. Please visit us at Booth #75 if you are able to attend the event.
The Oxford Nanopore sponsored industry symposium Accelerating precision oncology research with nanopore sequencing will take place on Tuesday 11th June in the Port Room at 08:30 - 09:15 hrs (CET).
Register below and join the session in good time to take your seat. Seats allocated on a first come first serve basis.
Symposium summary: Native, PCR-free nanopore sequencing, with unrestricted read lengths, offers a unique view into cancer biology. This allows the identification of single nucleotide variants, structural variants, and epigenetic modifications on a haplotype level — from a single dataset. In this session, we’ll explore how these technical benefits open up a new window of understanding into cancer genomes, featuring projects ranging from cancer whole-genome sequencing and targeted sequencing assays to cell-free DNA sequencing with methylation calling.
Speakers
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Christophe Fleury, Oxford Nanopore TechnologiesBackground / Objectives: The identification of germline alterations is a fundamental aspect of oncogenetics. While Next Generation Sequencing has accelerated the detection of nucleotide variants, the characterization of structural variants (SV) remains a challenge, often requiring time-consuming analyses. This report aims to establish the proof of concept that Nanopore adaptive sampling serves as an effective tool for exploring SVs with direct implications for clinical practice. Methods: Each DNA library is prepared in half a day without complex preparation steps. By detecting ionic potential changes as the DNA molecule passes through a biological nanopore, it enables real-time long-read sequencing. With adaptive sampling, the bioinformatics selection of genomic regions of interest using the MinKnow interface allows significant reading enrichment on those targeted regions. Downstream analyses are performed using the NanoClid pipeline, developed by the bioinformatics unit and available on GitHub (https://github.com/InstituteCurieClinicalBioinformatics/NanoCliD ). Results: Through the presentation of five clinical cases, we demonstrate that Nanopore adaptive sequencing allowed the germline SV characterization in cancer predisposition genes, such as BRCA1, RAD51C, MSH6 or SMARCB1. The speed of response (below 15 days) offered by Nanopore technology has a major impact on the immediate patient’s management. Conclusion: Nanopore sequencing unique features allow adaptive sampling which appears as a simple and fast technique to resolve SV that conventional short read sequencing techniques were unable to characterize, in a timeframe compatible with clinical decisions.
Background / Objectives: The identification of germline alterations is a fundamental aspect of oncogenetics. While Next Generation Sequencing has accelerated the detection of nucleotide variants, the characterization of structural variants (SV) remains a challenge, often requiring time-consuming analyses. This report aims to establish the proof of concept that Nanopore adaptive sampling serves as an effective tool for exploring SVs with direct implications for clinical practice. Methods: Each DNA library is prepared in half a day without complex preparation steps. By detecting ionic potential changes as the DNA molecule passes through a biological nanopore, it enables real-time long-read sequencing. With adaptive sampling, the bioinformatics selection of genomic regions of interest using the MinKnow interface allows significant reading enrichment on those targeted regions. Downstream analyses are performed using the NanoClid pipeline, developed by the bioinformatics unit and available on GitHub (https://github.com/InstituteCurieClinicalBioinformatics/NanoCliD ). Results: Through the presentation of five clinical cases, we demonstrate that Nanopore adaptive sequencing allowed the germline SV characterization in cancer predisposition genes, such as BRCA1, RAD51C, MSH6 or SMARCB1. The speed of response (below 15 days) offered by Nanopore technology has a major impact on the immediate patient’s management. Conclusion: Nanopore sequencing unique features allow adaptive sampling which appears as a simple and fast technique to resolve SV that conventional short read sequencing techniques were unable to characterize, in a timeframe compatible with clinical decisions.
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Mathilde Filser, Curie InstituteMultiple myeloma (MM), a genetically highly heterogeneous type of cancer that forms in plasma cells, is the second most frequent hematologic malignancy. As is the case with many types of cancer, next-generation sequencing technologies have opened the door to great advances in the fight against it. There is increasing evidence, however, that many important genomic events, like certain types of structural variation or DNA base modifications, are harder or even impossible to study with short-read based, next-generation sequencing technologies. Taking advantage of the latest advances in nanopore sequencing, we’re studying the evolution of MM using a collection of genomic approaches that are now more comprehensive, easier to perform, and cost-effective. We have sequenced a multi-drug-resistant MM cell line at different time points of resistance acquisition, as well as three clinical cases that developed resistance to a variety of both standard treatments and novel immunotherapies, including one that has developed multi-drug resistance. The cases' diverse treatment histories and responses to treatment provide a unique opportunity to develop insights into the elusive mechanisms of drug resistance. This research aims at expanding our understanding of multiple myeloma, potentially propelling us towards more individualized treatment plans and innovative strategies to counteract drug resistance and improving overall therapeutic outcomes.
Multiple myeloma (MM), a genetically highly heterogeneous type of cancer that forms in plasma cells, is the second most frequent hematologic malignancy. As is the case with many types of cancer, next-generation sequencing technologies have opened the door to great advances in the fight against it. There is increasing evidence, however, that many important genomic events, like certain types of structural variation or DNA base modifications, are harder or even impossible to study with short-read based, next-generation sequencing technologies. Taking advantage of the latest advances in nanopore sequencing, we’re studying the evolution of MM using a collection of genomic approaches that are now more comprehensive, easier to perform, and cost-effective. We have sequenced a multi-drug-resistant MM cell line at different time points of resistance acquisition, as well as three clinical cases that developed resistance to a variety of both standard treatments and novel immunotherapies, including one that has developed multi-drug resistance. The cases' diverse treatment histories and responses to treatment provide a unique opportunity to develop insights into the elusive mechanisms of drug resistance. This research aims at expanding our understanding of multiple myeloma, potentially propelling us towards more individualized treatment plans and innovative strategies to counteract drug resistance and improving overall therapeutic outcomes.
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Tomás Di Domenico, Spanish National Cancer Research Centre (CNIO)
