Clinical utility of 'Shaken' biopsies for whole-genome sequencing.

Aims: Whole-genome sequencing (WGS) is beginning to be applied to cancer samples in the clinical setting. This ideally requires high-quality, minimally degraded DNA of high tumour cell content, while retaining sufficient tissue with excellent morphology for histopathological diagnosis and immunohistochemistry. The aim of this study was to investigate alternative ways of handling cancer samples to fulfil both diagnostic and molecular requirements.

Methods: Ex vivo biopsies were taken to investigate the feasibility of using cancer cells 'shaken' from the surface of a biopsy for WGS, while maintaining the tissue biopsy for histological diagnosis. WGS from the shaken cells was compared with the gold standard of a fresh-frozen (FF) biopsy. The procedure was piloted in the real-world setting for breast cancer samples.

Results: Cells shaken from ex vivo biopsies can yield DNA of sufficient quantity and quality for WGS, while having no discernible impact on quality of tissue morphology. WGS data showed good coverage, comparable variant calls and generally higher tumour content in shaken cell samples compared with the control FF samples. For real-world biopsies, DNA yields were lower, but WGS data were of excellent quality for the cases analysed.

Conclusions: Shaken biopsy sampling allows genomic sequencing from patients with cancer who may otherwise not receive a genome sequence due to limited sample availability. It represents a way of overcoming the logistics of obtaining and storing FF tissue making it a suitable technique for wider scale implementation in the clinical setting.