GRCh38 · COSMIC v94


This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Extensive heterogeneity in somatic mutation and selection in the human bladder.
Paper ID
Lawson ARJ, Abascal F, Coorens THH, Hooks Y, O'Neill L, Latimer C, Raine K, Sanders MA, Warren AY, Mahbubani KTA, Bareham B, Butler TM, Harvey LMR, Cagan A, Menzies A, Moore L, Colquhoun AJ, Turner W, Thomas B, Gnanapragasam V, Williams N, Rassl DM, Vöhringer H, Zumalave S, Nangalia J, Tubío JMC, Gerstung M, Saeb-Parsy K, Stratton MR, Campbell PJ, Mitchell TJ and Martincorena I
Cancer, Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Hinxton CB10 1SA, UK.
Science (New York, N.Y.), 2020;370(6512):75-82
ISSN: 1095-9203
PMID: 33004514 (view at PubMed or Europe PMC)
The extent of somatic mutation and clonal selection in the human bladder remains unknown. We sequenced 2097 bladder microbiopsies from 20 individuals using targeted (<i>n</i> = 1914 microbiopsies), whole-exome (<i>n</i> = 655), and whole-genome (<i>n</i> = 88) sequencing. We found widespread positive selection in 17 genes. Chromatin remodeling genes were frequently mutated, whereas mutations were absent in several major bladder cancer genes. There was extensive interindividual variation in selection, with different driver genes dominating the clonal landscape across individuals. Mutational signatures were heterogeneous across clones and individuals, which suggests differential exposure to mutagens in the urine. Evidence of APOBEC mutagenesis was found in 22% of the microbiopsies. Sequencing multiple microbiopsies from five patients with bladder cancer enabled comparisons with cancer-free individuals and across histological features. This study reveals a rich landscape of mutational processes and selection in normal urothelium with large heterogeneity across clones and individuals.
Paper Status