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Next generation sequencing to enhance initial staging and dynamically monitor disease response in upper tract urothelial carcinoma

Funder: Bladder Cancer Advocacy Network

Funding period
USD 50 K
Funding amount
Abstract
Background: Current approaches to assessing clinical grade and stage in upper tract urothelial carcinoma (UTUC) have well-known limitations, sometimes leading to suboptimal assignment of therapy. Therefore, a urinary DNA (uDNA) next generation sequencing (NGS) biomarker test was developed for the purpose of enhanced clinical staging and grading using urine collected from patients with UTUC who underwent RNU.Hypotheses: (i) Mutations in UTUC tumor tissue (MT) are detectable in uDNA. (ii) Persistence of MU in the post-neoadjuvant uDNA will correlate with the presence of residual disease in the pathologic RNU specimen. (iii) Mutations which are specific to high stage or high grade disease will be detectable in the uDNA and correlate with pathological stage and grade of UTUC.Aims: (i) To correlate presence of MT with mutations in uDNA (MU). (ii) To correlate MU persistence status with nonresponder status. (iii) To correlate MU to pathological stage and grade in RNU specimens.Methodology: uDNA will be deep sequenced from 145 patients using a panel of 50 relevant genes. All patients underwent RNU ± neoadjuvant chemotherapy. Biomarker performance will be characterized against well-annotated benchmarks. pCR status and grade and stage of disease will be correlated to biomarker readouts using Fisher’s exact test. Preliminary data: uDNA was sequenced in 18 patients (12 with muscle-invasive bladder cancer, 6 with UTUC). The biomarker detected 61% of known mutations, had a 94% accuracy in assigning responder status, and identified high grade UTUC in 5/6 patients.Applicability to patients with urothelial cancer: Successful development of this biomarker test will significantly enhance the clinician’s capacity to accurately stage and grade UTUC extent.

 
8
Projects
USD 788 K
Aggregated funding amount
USD 98 K
Average funding amount
Project list item
Upper tract urothelial carcinoma is non-basal and T-cell depleted

Bladder Cancer Advocacy Network to Panagiotis Vlachostergios

USD 1,700
2018 - 2018
Project list item
Ascertaining the role of mutations in COMPASS-like complex members in the development of upper tract urothelial carcinoma

Bladder Cancer Advocacy Network to Byron H Lee, Nima Sharifi, Ming Hu, Daniel Kim

USD 50,000
2017 - 2018
Project list item
The likelihood of underlying Lynch syndrome in upper tract urothelial carcinoma patients

Japan Society for the Promotion of Science to Masaya ITO

USD 21,145
2016 - 2018
Project list item
Epithelial to mesenchymal transition thorough GEP100-Arf6-AMAP1 pathway in urothelial cancer

Japan Society for the Promotion of Science to Tatsuaki Daimon

USD 34,348
2015 - 2017
Project list item
Investigation of anti-tumor effect of Axl kinase inhibitor in urothelial carcinoma.

Japan Society for the Promotion of Science to Seiya Hattori

USD 33,260
2014 - 2016
Project list item
Staging of upper tract urothelial cancer with optical coherence tomography

National Cancer Institute to ANDREW MARTIN ROLLINS, HUI ZHU

USD 548,995
2012 - 2015
Project list item
Risk group stratification to predict prognosis in Japanese patients with urothelial carcinoma

Japan Society for the Promotion of Science to Shigeru SAKANO

USD 52,673
2012 - 2015
Project list item
The efficacy of renin-angiotensin system blockade for upper tract urothelial carcinoma

Japan Society for the Promotion of Science to Nobuyuki TANAKA

USD 45,791
2012 - 2014