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• W3007868408 abstract "538 Background: Nested variant urothelial carcinoma (NVUC) is a historically aggressive variant of bladder cancer with management reliant on radical cystectomy given unclear effectiveness of chemotherapy. Given the aggressive behavior of NVUC, the identification of pathogenic and potentially targetable genomic alterations could suggest novel treatment paradigms for this rare histologic variant. Methods: Query of our institutional database identified 81 cases of clinically localized NVUC. Each case was re-reviewed by GU pathologists to confirm the histology. Targeted capture sequencing was performed to define the spectrum of genomic alterations in known and putative cancer genes. Clinical and sequencing data was then compared between the nested variant cases and a prospective cohort of clinically localized high-grade urothelial carcinomas, not otherwise specified (UC NOS). Results: On central re-review, tumors were classified as either classic NVUC (N=53) or high-grade urothelial carcinoma with nested features (N=28). A cohort of UC NOS patients (N=600) was used as a comparator. Median follow-up of the overall cohort was 4.3 years. Classic NVUC was associated with higher risk of cancer specific mortality compared to UC NOS on multivariate analysis (HR 1.76, p=0.04). Tumor mutational burden was lower in classic NVUC tumors versus UC NOS. Evaluation of 136 cancer-associated genes identified differences in mutational frequencies across the 3 cohorts (Table) with RhoA and FOXA1 alterations enriched in NVUC. Conclusions: Patients with NVUC have significantly higher risk of cancer specific mortality than patients with UC NOS. While there was significant overlap between the landscape of genomic alterations in NVUC and UC NOS tumors, NVUC tumors were enriched for RhoA and FOXA1 alterations among others.[Table: see text]" @default.
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• W3007868408 date "2020-02-20" @default.
• W3007868408 modified "2023-09-27" @default.
• W3007868408 title "Genomic determinants of nested variant urothelial carcinoma." @default.
• W3007868408 doi "https://doi.org/10.1200/jco.2020.38.6_suppl.538" @default.
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