London Calling 2023: The potential of nanopore sequencing for personalised oncogenomics

Since 2012, our centre has run a successful personalised oncogenomics (POG) trial for patients with advanced cancers using short-read sequencing technology for whole-genome and transcriptome analysis of tumours to inform clinical decisions. Nanopore sequencing offers improved structural variant (SV) resolution, phasing, and methylation information. We have sequenced 187 cases from the POG trial on a PromethION, including 39 with matching normal tissue. We were able to detect clinically relevant structural variants previously known from Illumina, despite lower coverage, and to decipher complex SVs. Phasing allowed us to detect allele-specific expression and methylation, as well as whether multiple hits to the same gene were cis or trans. Methylation allowed us to cluster tumours by type and extract a coarse-level view of the tumour microenvironment using MethylCIBERSORT. We will release our data via the European Genomics Archive to serve as a test bed for tool development in tumour characterization.