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.

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

Children with cancer at relapse or initial diagnosis