Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden

J. -B. Cazier, S. R. Rao, C. M. McLean, A. K. Walker, B. J. Wright, E. E. M. Jaeger, C. Kartsonaki, L. Marsden, C. Yau, C. Camps, P. Kaisaki, J. Taylor, J. W. Catto, I. P. M. Tomlinson (), A. E. Kiltie and F. C. Hamdy
Additional contact information
J. -B. Cazier: Bioinformatics Group, University of Oxford
S. R. Rao: Botnar Research Centre, University of Oxford
C. M. McLean: Cancer Research UK, Oxford Cancer Research Centre, University of Oxford
A. K. Walker: Cancer Research UK, Oxford Cancer Research Centre, University of Oxford
B. J. Wright: Bioinformatics and Statistical Genetics Core, Wellcome Trust Centre for Human Genetics
E. E. M. Jaeger: Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics
C. Kartsonaki: Bioinformatics Group, University of Oxford
L. Marsden: Cancer Research UK, Oxford Cancer Research Centre, University of Oxford
C. Yau: Yau Group, Wellcome Trust Centre for Human Genetics
C. Camps: NIHR Comprehensive Biomedical Research Centre, Wellcome Trust Centre for Human Genetics
P. Kaisaki: NIHR Comprehensive Biomedical Research Centre, Wellcome Trust Centre for Human Genetics
J. Taylor: NIHR Comprehensive Biomedical Research Centre, Wellcome Trust Centre for Human Genetics
J. W. Catto: Academic Urology Unit, University of Sheffield
I. P. M. Tomlinson: Cancer Research UK, Oxford Cancer Research Centre, University of Oxford
A. E. Kiltie: Cancer Research UK, Oxford Cancer Research Centre, University of Oxford
F. C. Hamdy: Cancer Research UK, Oxford Cancer Research Centre, University of Oxford

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former are not mutually exclusive with TP53 mutations or MDM2 amplification, showing that CDKN1A dysfunction is not simply an alternative mechanism for p53 pathway inactivation. We find strong positive associations between higher tumour stage/grade and greater clonal diversity, the number of somatic mutations and the burden of copy number changes. In principle, the identification of sub-clones with greater diversity and/or mutation burden within early-stage or low-grade tumours could identify lesions with a high risk of invasive progression.

Date: 2014
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms4756 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4756

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms4756

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().