CLINICAL whole-genome sequencing (WGS) of children with cancer demonstrated significant benefits, leading to improved patient management and treatment decisions. The clinical benefits of WGS in paediatric oncology have been linked to the concept that genetic features often guide childhood cancer treatment. Moreover, the genetics of some types of childhood cancer are unexplored, meaning there is a potential for the identification of clinically significant variants. WGS has been previously shown to deliver potential benefits in cancer management for children in high-risk patient groups, even when standard-of-care testing includes expansive molecular assays. Nevertheless, there is an absence of data demonstrating the benefit of routine cancer WGS in pediatric practice. This study evaluated the impact of WGS at Great Ormond Street Hospital in London and Cambridge University Hospital, where WGS has become a routine test for clinical and diagnostic information.
Researchers conducted an observational study involving 281 children from two tertiary childhood cancer centres in England. Findings revealed that WGS led to immediate changes in clinical management for approximately 7% of cases (20 out of 282 tumours) by identifying unique variants. Additionally, WGS provided further disease-relevant findings beyond standard tests in 29% of cases (83 out of 281 children), aiding in the understanding and future care of these patients. WGS also proved capable of replicating every standard-of-care molecular test (totalling 738) used in these patients, suggesting that WGS could replace these conventional tests. This comprehensive genomic approach unveiled several previously unknown features of childhood tumours, highlighting the potential for more precise and informed patient care.
The results led study authors to conclude that WGS can be seamlessly integrated into routine clinical care, offering crucial genomic insights that standard molecular tests may miss. WGS was able to improve patient management as a routine clinical test. Furthermore, as most children in the patient cohorts did not have high-risk diseases, the results indicate that WGS may be helpful to all children with a neoplastic disorder. However, the researchers noted that NHS England utilises localised decision-making and clinical variant interpretation within the specific clinical context of children. Therefore, the results obtained may be specific to the tertiary centres included in the study. Regardless, the authors emphasised that genetic information is the ‘backbone’ of childhood cancer treatment and, thus, the benefits of routine WGS are likely broadly applicable.
Laith Gergi, EMJ
Reference:
Hodder A et al. Benefits for children with suspected cancer from routine whole-genome sequencing. Nat Med. 2024;DOI:10.1038/s41591-024-03056-w.
