@article{4d9539e529e74e18bf2c9abc769e54bb,
title = "Stage-stratified molecular profiling of non-muscle-invasive bladder cancer enhances biological, clinical, and therapeutic insight",
abstract = "Understanding the molecular determinants that underpin the clinical heterogeneity of non-muscle-invasive bladder cancer (NMIBC) is essential for prognostication and therapy development. Stage T1 disease in particular presents a high risk of progression and requires improved understanding. We present a detailed multi-omics study containing gene expression, copy number, and mutational profiles that show relationships to immune infiltration, disease recurrence, and progression to muscle invasion. We compare expression and genomic subtypes derived from all NMIBCs with those derived from the individual disease stages Ta and T1. We show that sufficient molecular heterogeneity exists within the separate stages to allow subclassification and that this is more clinically meaningful for stage T1 disease than that derived from all NMIBCs. This provides improved biological understanding and identifies subtypes of T1 tumors that may benefit from chemo- or immunotherapy.",
keywords = "NMIBC, PPAR gamma, classification, clinical outcome, copy number, genomics, non-muscle-invasive bladder cancer, stage T1, stage Ta, transcriptomics",
author = "Hurst, {Carolyn D.} and Guo Cheng and Platt, {Fiona M.} and Castro, {Mauro A. A.} and Marzouka, {Nour-al-dain S.} and Pontus Eriksson and Black, {Emma V. I.} and Olivia Alder and Lawson, {Andrew R. J.} and Lindskrog, {Sia V.} and Burns, {Julie E.} and Sunjay Jain and Jo-An Roulson and Brown, {Joanne C.} and Jan Koster and Robertson, {A. Gordon} and Inigo Martincorena and Lars Dyrskj{\o}t and Mattias H{\"o}glund and Knowles, {Margaret A.}",
note = "Funding Information: We thank Dmitry Gordenin for helpful discussions of mutational signatures and Matthieu Rederstorff for advice on snoRNA expression. We are indebted to all individuals who gave consent for their samples to be used. This work was funded by Yorkshire Cancer Research ( L376PA ) and Cancer Research UK ( C57387/A21777 ). Funding Information: We thank Dmitry Gordenin for helpful discussions of mutational signatures and Matthieu Rederstorff for advice on snoRNA expression. We are indebted to all individuals who gave consent for their samples to be used. This work was funded by Yorkshire Cancer Research (L376PA) and Cancer Research UK (C57387/A21777). Conceptualization, C.D.H. and M.A.K.; methodology, C.D.H. G.C. F.M.P. M.A.A.C. N.-a.-d.S.M. P.E. A.R.J.L. S.V.L. J.K. A.G.R. I.M. and M.A.K.; software, M.A.A.C. N.-a.-d.S.M. P.E. A.R.J.L. S.V.L. A.G.R. and I.M.; formal analysis, C.D.H. G.C. F.M.P. M.A.A.C. N.-a.-d.S.M. P.E. O.A. A.R.J.L. S.V.L. and M.A.K.; investigation, C.D.H. G.C. F.M.P. E.V.I.B. O.A. and J.E.B.; resources, S.J. J.-A.R. J.C.B. J.K. I.M. L.D. and M.H.; data curation, C.D.H. G.C. F.M.P. and J.C.B.; writing ? original draft, C.D.H. G.C. M.A.A.C. N.-a.-d.S.M. S.V.L. and M.A.K.; writing ? review & editing, all authors; supervision, M.A.K.; project administration, M.A.K.; funding acquisition, M.A.K. S.J. and J.-A.R. M.A.K. has an advisory/consulting role at Janssen, LOXO Oncology, QED, and Rainier Therapeutics. L.D. has sponsored research agreements with C2i-genomics, Natera, AstraZeneca, and Ferring and an advisory/consulting role at Ferring. L.D. has received a speaker honorarium from Roche. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = dec,
day = "21",
doi = "https://doi.org/10.1016/j.xcrm.2021.100472",
language = "English",
volume = "2",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "12",
}