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. 2024 Dec;131(11):1805-1813.
doi: 10.1038/s41416-024-02890-6. Epub 2024 Oct 30.

The potential clinical utility of Whole Genome Sequencing for patients with cancer: evaluation of a regional implementation of the 100,000 Genomes Project

Elaine Y L Leung #  1 , Helen L Robbins #  2 , Shafquat Zaman  1 , Neeraj Lal  1 , Dion Morton  3 , Lisa Dew  4 , Anthony P Williams  5 , Yvonne Wallis  6 , Jennie Bell  6 , Manoj Raghavan  2 , Gary Middleton  2 , Andrew D Beggs  7
Affiliations

The potential clinical utility of Whole Genome Sequencing for patients with cancer: evaluation of a regional implementation of the 100,000 Genomes Project

Elaine Y L Leung et al. Br J Cancer. 2024 Dec.

Abstract

Background: The 100,000 Genomes Project established infrastructure for Whole Genome Sequencing (WGS) in the United Kingdom.

Methods: A retrospective study of cancer patients recruited to the 100,000 Genomes Project by the West Midlands Genomics Medicine Centre, evaluating clinical relevance of results.

Results: After excluding samples with no sequencing data (1678/4851; 34.6%), 3166 sample sets (germline and somatic) from 3067 participants were sequenced. Results of 1256 participants (41.0%) were interpreted (excluding participants who died (308/3067; 10.0%) or were clinically excluded (1503/3067; 49.0%)). Of these, 323 (25.7%) had no variants in genes which may alter management (Domain 1 genes). Of the remaining 933 participants, 552 (59.2%) had clinical recommendations made (718 recommendations in total). These included therapeutic recommendations (377/933; 40.4%), such as clinical trial, unlicensed or licensed therapies or high TMB recommendations, and germline variants warranting clinical genetics review (85/933; 9.1%). At the last follow up, 20.2% of all recommendations were followed (145/718). However, only a small proportion of therapeutic recommendations were followed (5.1%, 25/491).

Conclusions: The 100,000 Genomes Project has established infrastructure and regional experience to support personalised cancer care. The majority of those with successful sequencing had actionable variants. Ensuring GTAB recommendations are followed will maximise benefits for patients.

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Conflict of interest statement

Competing interests: ADB receives laboratory support and consultancy fees from Illumina Inc and Oxford Nanopore. Ethical approval and consent to participate: The current work is a retrospective analysis of participants enroled in the 100,000 genome project in the West Midlands. All data analysed was routinely collected as part of the 100,000 genome project. The 100,000 genome project was approved by the HRA Committee East of England Cambridge South (REC Ref 14/EE/1112). All participants provided written informed consent. All work was conducted in accordance with relevant guidelines and regulations, including Good Clinical Practice and the Declaration of Helsinki’s ethical principles for medical research.

Figures

Fig. 1
Fig. 1. A flow chart summarising the number of participants and the outcomes after therapeutic recommendations.
*Multiple recommendations per participants were made for a proportion of this cohort. TR= Therapeutic recommendations (clinical trial, unlicensed or licensed therapies or high TMB).
Fig. 2
Fig. 2
A summary of stated reasons when samples were not sent for sequencing over time (n = 1669)*.
Fig. 3
Fig. 3
Proportions of recommendations followed, based on the type of recommendation (n = 718).
See this image and copyright information in PMC

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