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Molecular classification and diagnostics of upper urinary tract urothelial carcinoma.
- Source :
-
Cancer cell [Cancer Cell] 2021 Jun 14; Vol. 39 (6), pp. 793-809.e8. - Publication Year :
- 2021
-
Abstract
- Upper urinary tract urothelial carcinoma (UTUC) is one of the common urothelial cancers. Its molecular pathogenesis, however, is poorly understood, with no useful biomarkers available for accurate diagnosis and molecular classification. Through an integrated genetic study involving 199 UTUC samples, we delineate the landscape of genetic alterations in UTUC enabling genetic/molecular classification. According to the mutational status of TP53, MDM2, RAS, and FGFR3, UTUC is classified into five subtypes having discrete profiles of gene expression, tumor location/histology, and clinical outcome, which is largely recapitulated in an independent UTUC cohort. Sequencing of urine sediment-derived DNA has a high diagnostic value for UTUC with 82.2% sensitivity and 100% specificity. These results provide a solid basis for better diagnosis and management of UTUC.<br />Competing Interests: Declaration of interests D.B.S. has consulted with and received honoraria from Pfizer, Loxo/Lilly Oncology, Vividion Therapeutics, Scorpion Therapeutics and BridgeBio.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Aged
Biomarkers, Tumor genetics
Carcinoma, Transitional Cell mortality
DNA Methylation
Female
Gene Dosage
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Mutation
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins c-mdm2 genetics
Receptor, Fibroblast Growth Factor, Type 3 genetics
Tumor Suppressor Protein p53 genetics
Ureteral Neoplasms mortality
ras Proteins genetics
Biomarkers, Tumor urine
Carcinoma, Transitional Cell diagnosis
Carcinoma, Transitional Cell genetics
Ureteral Neoplasms diagnosis
Ureteral Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3686
- Volume :
- 39
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 34129823
- Full Text :
- https://doi.org/10.1016/j.ccell.2021.05.008