Ultrafast Whole Genome Sequencing for Childhood Cancer (UF-WGS)

Feasibility of Ultrafast WGS in Paediatric Malignancies

Cambridge University Hospitals NHS Foundation Trust (CUHNFT) is the Principal Treatment Centre for the East of England region, responsible for 120-150 patients <16 years with a new diagnosis of paediatric malignancy annually; leukaemia comprises ~25% of these cases. Current molecular diagnosis of subgroups of childhood malignancies, particularly leukaemia, is based on flow cytometry, fluorescent in situ hybridisation (FISH) and single nucleotide polymorphim (SNP) arrays, for which the usual turnaround time (TAT) is 7-14 days. In the current era of access to targeted therapy, rapid diagnosis and treatment of patients in high-risk molecular subgroups is critical for improving outcomes. Children and adolescents with Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL) have significantly improved survival when treated with tyrosine kinase inhibitors (TKIs). Patients with Ph+-like mutations (10- 20% of paediatric ALL), also have a poor prognosis, requiring escalation of treatment and addition of targeted therapy. Rapidly identifying MYCN amplification is also of critical prognostic importance in embryonal tumours of childhood including neuroblastoma (25%) and medulloblastoma, and directly impacts on treatment from the outset of the patient journey. Overnight whole genome sequencing (WGS) entails taking an additional 5ml Peripheral Blood (PB) and Bone Marrow (BM) samples after samples for routine diagnostic workup have been collected, and could replace current standard of care (SOC), which has a median turnaround time (TAT) of up to 28 days, and up to 84 days for specific gene mutations, which can delay appropriate prognostication and management of high-risk patients. Rapid, point of care information on somatic and germline mutations will allow early risk stratification and expedite treatment for high-risk patients with cancer.

Study Overview

• Status: Recruiting
• Conditions: Cancer Childhood

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Victoria Joslin; Phone Number: 01223217251; Email: vicky.joslin@nhs.net

Study Locations

• United Kingdom
  • Cambridge, United Kingdom
    • Recruiting
    • Addenbrookes Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children with cancer at relapse or initial diagnosis

Description

Inclusion Criteria:

• Have given written informed consent to participate
• Be aged <25 years of age
• Have confirmed or suspected malignancy
• For pilot/feasibility study (first 10 patients), only haematological malignancies (ALL/AML) will be included
• Have tumour and germline sample available - retrospectively collected or for prospective collection

Exclusion Criteria:

• Inability to provide written informed consent (self or parent/guardian)
• Insufficient tissue (BM/PB/tissue) available for research purposes after collection for routine diagnostic purposes

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Ultrafast WGS cohort, prospective patients
Ultrafast WGS, retrospective patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Turnaround time from sample collection to availability of meaningful results.	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of enrolled patients with available WGS results from the Ultrafast WGS pipeline.	24 months
Correlation of data from Ultrafast WGS against current SOC WGS data.	36 months

Collaborators and Investigators

• Sponsor: University of Cambridge
• Collaborators: Cambridge University Hospitals NHS Foundation Trust; Illumina, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2022
• Primary Completion (Estimated): October 18, 2027
• Study Completion (Estimated): October 17, 2028

Study Registration Dates

• First Submitted: September 23, 2025
• First Submitted That Met QC Criteria: September 23, 2025
• First Posted (Actual): October 1, 2025

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: whole genome sequencing
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: IRAS317008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No