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GRIFFIN, Jon, DOWN, Jenny, QUAYLE, Lewis, HEATH, Paul R, GIBB, Ewan A, DAVICIONI, Elai, LIU, Yang, ZHAO, Xin, SWAIN, Jayne, WANG, Dennis, HUSSAIN, Syed, CRABB, Simon and CATTO, James WF (2024). Verification of molecular subtyping of bladder cancer in the GUSTO clinical trial. The Journal of Pathology: Clinical Research, 10 (2): e12363.
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Abstract
The GUSTO clinical trial (Gene expression subtypes of Urothelial carcinoma: Stratified Treatment and Oncological outcomes) uses molecular subtypes to guide neoadjuvant therapies in participants with muscle‐invasive bladder cancer (MIBC). Before commencing the GUSTO trial, we needed to determine the reliability of a commercial subtyping platform (Decipher Bladder; Veracyte) when performed in an external trial laboratory as this has not been done previously. Here, we report our pre‐trial verification of the TCGA molecular subtyping model using gene expression profiling. Formalin‐fixed paraffin‐embedded tissue blocks of MIBC were used for gene expression subtyping by gene expression microarrays. Intra‐ and inter‐laboratory technical reproducibilities, together with quality control of laboratory and bioinformatics processes, were assessed. Eighteen samples underwent analysis. RNA of sufficient quality and quantity was successfully extracted from all samples. All subtypes were represented in the cohort. Each sample was subtyped twice in our laboratory and once in a separate reference laboratory. No clinically significant discordance in subtype occurred between intra‐ or inter‐laboratory replicates. Examination of sample histopathology showed variability of morphological appearances within and between subtypes. Overall, these results show that molecular subtyping by gene expression profiling is reproducible, robust and suitable for use in the GUSTO clinical trial.
| Item Type: | Article |
|---|---|
| Additional Information: | ** Article version: VoR ** From Wiley via Jisc Publications Router ** Licence for VoR version of this article: http://creativecommons.org/licenses/by/4.0/ **Journal IDs: issn 2056-4538 **Article IDs: publisher-id: cjp212363 **History: published 03-2024; published_online 01-02-2024; accepted 08-01-2024; rev-recd 23-11-2023; submitted 14-09-2023 |
| Uncontrolled Keywords: | molecular pathology, gene expression subtypes, urothelial carcinoma |
| Identification Number: | https://doi.org/10.1002/2056-4538.12363 |
| SWORD Depositor: | Colin Knott |
| Depositing User: | Colin Knott |
| Date Deposited: | 02 Feb 2024 15:19 |
| Last Modified: | 02 Feb 2024 15:30 |
| URI: | https://shura.shu.ac.uk/id/eprint/33119 |
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