biostudies-literatureMitchell JAssociazione Italiana per la Ricerca sul CancroWellcome Trust323https://www.ebi.ac.uk/biostudies/studies/S-EPMC10796348biostudies-literatureUnknown15(1)The unexpected contamination of normal samples with tumour cells reduces variant detection sensitivity, compromising downstream analyses in canonical tumour-normal analyses. Leveraging whole-genome sequencing data available at Genomics England, we develop a tool for normal sample contamination assessment, which we validate in silico and against minimal residual disease testing. From a systematic review of [Formula: see text] patients with haematological malignancies and sarcomas, we find contamination across a range of cancer clinical indications and DNA sources, with highest prevalence in saliva samples from acute myeloid leukaemia patients, and sorted CD3+ T-cells from myeloproliferative neoplasms. Further exploration reveals 108 hotspot mutations in genes associated with haematological Nature communicationsClinical application of tumour-in-normal contamination assessment from whole genome sequencing.PMC1079634824913Mitchell JBartram JYavorska OThomas RVago LCaravagna GWalker SVolkova NZarowiecki MSosinsky AChalker JMilite SfalseClinical application of tumour-in-normal contamination assessment from whole genome sequencing.The unexpected contamination of normal samples with tumour cells reduces variant detection sensitivity, compromising downstream analyses in canonical tumour-normal analyses. Leveraging whole-genome sequencing data available at Genomics England, we develop a tool for normal sample contamination assessment, which we validate in silico and against minimal residual disease testing. From a systematic review of [Formula: see text] patients with haematological malignancies and sarcomas, we find contamination across a range of cancer clinical indications and DNA sources, with highest prevalence in saliva samples from acute myeloid leukaemia patients, and sorted CD3+ T-cells from myeloproliferative neoplasms. Further exploration reveals 108 hotspot mutations in genes associated with haematological 2024-01-01T00:00:00Z2024 Jan2026-06-03T14:27:13.835Z2025-04-04T19:22:23.016ZS-EPMC107963483823829410.1038/s41467-023-44158-2