In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 2188-2188
Abstract:
The UC-GENOME study was designed to capitalize on The Cancer Genome Atlas (TCGA) findings in real world patients with metastatic urothelial carcinoma (UC) with co-equal aims: 1) to provide targeted DNA sequencing for potential clinical decision making at no cost to patients; and 2) to create a clinically annotated biorepository (including tissue, plasma, and PBMCs) for collaborative research. Patients with metastatic UC (n=209, median age 68 y, 74% male) were accrued at 8 academic medical centers between 2016-2019. We report on the first analysis of the targeted DNAseq (n=191) and total RNAseq (n=176) from FFPE specimens (n=169 overlap). Recurrently mutated genes were observed in a similar frequency to TCGA, including TP53 (54%), KMT2D (30%), ARID1A (26%) and FGFR3 (18%). Somatic variant patterns were correlated with previously annotated mutational signatures (COSMICv3), revealing a subset of tumors enriched for APOBEC signatures. Molecular subtypes were defined using the Bladder Cancer Molecular Taxonomy Group's consensus subtyping schema (Ba_Sq=54 [31%], Stroma-rich=64 [36%] , LumP=26 [15%], LumU=24 [14%] , LumNS=4 [2%], NE=4 [2%] ). To further understand the tumor immune features and whether they correlate with durable clinical response, tumor microenvironment deconvolution was performed by applying MiXCR and immune gene signatures. An inflamed phenotype and enhanced T cell receptor richness but not clonality was observed within Ba_Sq and Stroma-rich subtypes, which also had the highest disease control rate (CR/PR + SD ~75%) to immunotherapy. The Stroma-rich subtype had the highest disease control rate (~88%) to chemotherapy. Future efforts will leverage the clinical, DNA and RNAseq data along with other biobanked specimens for collaborative research initiatives. Citation Format: Jeffrey S. Damrauer, Jeff Klomp, Wolfgang Beck, Mi Zhou, Elizabeth Plimack, Matthew Galsky, Petros Grivas, Noah Hahn, Peter O'Donnell, Gopa Iyer, David I. Quinn, Katherine A. Hoadley, William Y. Kim, Matthew I. Milowsky. Urothelial cancer-GENOmic analysis to improve patient outcomes and research (UC-GENOME): a bladder cancer advocacy network (BCAN) led collaborative research study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2188.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2021-2188
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2021
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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