Lessons from AACR 2024
Every year at the American Association for Cancer Research (AACR) meeting the progress in cancer genomics never ceases to amaze. AACR 2024 was no different.
One talk covered how AI and liquid biopsies have the potential to detect ovarian cancer more accurately than other biomarkers. Another shared how accelerated aging was identified as a risk factor for the development of early-onset solid tumours which, if validated, provides a new line of investigation to develop precision cancer prevention strategies.
Meanwhile, research with nanopore technology provided every insight you can imagine, and then some. Read on for more.
Bigger and bolder research questions
On a pan-cancer level, about 50% of driver mutations can be explained by underlying structural variants (SVs). With short-read sequencing, algorithms are used to infer rearrangements, whereas long reads can cover the complete sequence of the variant and can be phased into paternal and maternal haplotypes, removing the risk of potential errors being introduced with the short-read algorithms.
Most long-read SV callers are not optimised for the analysis of cancer genomes, so, addressing this, Mikhail Kolmogorov and Ayse Keskus from the National Cancer Institute (National Institutes of Health) described Severus, their new tool for the analysis of matched tumour/normal and multi-site tumour data, to produce phased calls that can cluster and classify complex SVs. Benchmarking tests and analysis of canine osteosarcomas suggested that Severus is a high-accuracy workflow that can be implemented by other cancer researchers for their projects.
You can hear more from Mikhail on their canine osteosarcoma research from our NCM Houston meeting (2023).
Sequencing that keeps up with you
Julie Geyer highlighted the role that genomics plays in stratifying paediatric acute leukaemia, so that clinicians can assess risk and make informed decisions for their patients. Currently, three different tests may be required to classify paediatric acute leukaemia which is costly and time consuming. Julie and her colleagues are exploring the capacity to replace these tests using adaptive sampling on the PromethION 2 Solo to detect copy number variation, fusions, duplications, and deletions.
When their workflow was applied to 30 retrospective samples, gross karyotype abnormalities and fusion detections were identified with 100% consistency with the clinically determined results. When the workflow was applied to samples obtained in real-time, the wet-lab steps took 3 hours, fusion detection 3-6 hours, and digital karyotyping 10-15 minutes. Overall, nanopore sequencing was found to offer a rapid, cost-effective and reliable way to classify samples.
Revealing powerful information
In the poster hall there was a range of research presented demonstrating different applications of nanopore sequencing. Topics included transcriptomics, methylation detection, cell-free DNA analysis, telomere sequencing, single-cell sequencing, and the detection of variants, ranging from point mutations through to large structural rearrangements. Our Applications team joined and showcased the results from their latest cutting-edge projects:
- Translocation detection in cancer using low-pass pore-c sequencing
- Haplotype-resolved analysis of cancer genomes and epigenomes using Oxford Nanopore sequencing
- Native nanopore sequencing of multiple tumor sites reveals genetic and epigenetic intra-tumor heterogeneity in canine osteosarcoma
Comprehensive insights
With the complex and ever-changing genomic and epigenomic landscape of a tumour, researchers need sequencing that can keep up.
If you would be interested in participating in the beta testing programme of our new RUO comprehensive germline cancer end to end workflow, you can register your interest here. Or, read more about how nanopore sequencing can support your cancer research.
What's next?
This year’s AACR has been insightful, and we are putting the dates for the next meeting into our diaries already! If you can’t wait that long, please come and join us for our annual London Calling conference, held between 21-24th May, to find out how researchers are using nanopore sequencing to accelerate their cancer research.