The mutational and clonality profile of high-grade serous ovarian cancer is established early in tumour development and conserved throughout therapy resistance
The diversity of high-grade serous ovarian cancer (HGSOC) makes tracking tumour evolution challenging. Oxford Nanopore sequencing successfully phased ultra-long SVs, revealing that tumour evolution is driven by early clonal events rather than therapy-induced mutations. Despite shared mutational mechanisms, each person develops unique somatic mutations, supporting the need for a personalised medicine approach to cancer treatment.
Key points:
Tumour heterogeneity is believed to be a key feature of recurrence and resistance in HGSOC tumours
In matched primary and recurrent HGSOC tumours from 32 patients, Diaz and Gull et al. found that somatic mutation profiles remained largely conserved through disease progression
Chemoresistance likely arises from pre-existing clones rather than new mutations
Ultra-long reads generated by Oxford Nanopore sequencing validated SVs detected by short-read sequencing, but also uncovered novel SVs including large insertions, deletions, and complex rearrangements
SV analysis identified three distinct tumour subtypes, providing potential biomarkers for targeted treatment strategies in the future
Sample type: human ovarian cancer tumours