Thomas Mitchell

Jan 16, 2025 | nature.com | Sabrina Rossi |Laura Godfrey |Justicia Kyeremeh |Thomas Mitchell |Grant Stewart |Roland F. Schwarz

AbstractClear cell renal cell carcinoma (ccRCC) is characterised by significant genetic heterogeneity, which has diagnostic and prognostic implications. Very limited evidence is available regarding DNA methylation heterogeneity. We therefore generate sequence level DNA methylation data on 136 multi-region tumour and normal kidney tissue from 18 ccRCC patients, along with matched whole exome sequencing (85 samples) and gene expression (47 samples) data on a subset of samples.

Jul 6, 2023 | nature.com | Carolin M Sauer |Jose Espejo Valle-Inclan |Thomas Mitchell

AbstractCharacterization of somatic mutations at single-cell resolution is essential to study cancer evolution, clonal mosaicism and cell plasticity. Here, we describe SComatic, an algorithm designed for the detection of somatic mutations in single-cell transcriptomic and ATAC-seq (assay for transposase-accessible chromatin sequence) data sets directly without requiring matched bulk or single-cell DNA sequencing data.

Mar 8, 2023 | nature.com | Vincent Roberto Zecchini |Gonçalo Pereira |Laura Tronci |Shamith A. Samarajiwa |Thomas Mitchell |Julien Prudent | +1 more

AbstractMutations in fumarate hydratase (FH) cause hereditary leiomyomatosis and renal cell carcinoma1. Loss of FH in the kidney elicits several oncogenic signalling cascades through the accumulation of the oncometabolite fumarate2. However, although the long-term consequences of FH loss have been described, the acute response has not so far been investigated. Here we generated an inducible mouse model to study the chronology of FH loss in the kidney.