1207O - Beyond 100,000 genomes project: Whole genome sequencing for cancer patients within NHS Genomic Medicine Service

Background

The 100,000 Genomes Project was a transformational UK government initiative, conducted within the National Health Service (NHS) in England. The primary goal was to undertake Whole Genome Sequencing (WGS) for patients with cancer, rare disease and infectious diseases and standardise high throughput, automated bioinformatic analysis and interpretation. The NHS Genomic Medicine Service (GMS) was launched in 2019 to enable equitable access to genomic medicine and comprehensive genomic testing using a standardised National Genomic Test Directory (NGTD). Building on the work of the 100,000 Genomes Project, WGS is now offered as routine care through the GMS for specific clinical indications.

Methods

To validate the performance of the bioinformatics pipeline for WGS analysis across different variant and tumour types, we compared WGS analysis with other genomic tests commissioned through the NGTD. Data were collected by NHS genomic laboratories for 285 tumour samples for which WGS and orthogonal testing were performed (n=1,579 tests).

Results

87% of tests were considered by NHS laboratory scientists to be concordant with the WGS results. Critical review of 167 discordant tests revealed that discrepancies were most frequently due to limitations in somatic CNV detection by WGS (25%), tumour in normal contamination (12%) and variants that were detected as being germline from tumour-normal WGS but could not be classified accordingly from a tumour-only panel test (11%). We reviewed clinical actionability of WGS findings for 982 tumours. Clinically relevant findings are defined as variants associated with therapeutic response, diagnostic or prognostic classification or clinical trial eligibility. Based on the outcomes reported by NHS genomic laboratories, actionable variants were found for up to 90% of patients, depending on the tumour type. The types of actionable variants varied by tumour type with sarcoma patients having the highest proportion of actionable structural variants or copy number changes and paediatric solid tumour patients having the highest proportion of germline predisposition findings.

Conclusions

WGS is a reliable and comprehensive method for identifying clinically relevant variants in cancer genomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

NHS and Department of Health.

Disclosure

All authors have declared no conflicts of interest.