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Molecular Characterization of Upper Tract Urothelial Carcinoma in the Era of Next-generation Sequencing: A Systematic Review of the Current Literature
MR. Hassler, F. Bray, JWF. Catto, AP. Grollman, A. Hartmann, V. Margulis, SF. Matin, M. Roupret, JP. Sfakianos, SF. Shariat, BM. Faltas
Language English Country Switzerland
Document type Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Systematic Review
Grant support
NIHR300047
Department of Health - United Kingdom
- MeSH
- Molecular Diagnostic Techniques MeSH
- Carcinoma, Transitional Cell genetics MeSH
- Humans MeSH
- Kidney Neoplasms genetics MeSH
- Ureteral Neoplasms genetics MeSH
- High-Throughput Nucleotide Sequencing * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Systematic Review MeSH
CONTEXT: While upper tract urothelial carcinoma (UTUC) share histological appearance with bladder cancer (BC), the former has differences in etiology and clinical phenotype consistent with characteristic molecular alterations. OBJECTIVE: To systematically evaluate current genomic sequencing and proteomic data examining molecular alterations in UTUC. EVIDENCE ACQUISITION: A systematic review using PubMed, Scopus, and Web of Science was performed in December 2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. EVIDENCE SYNTHESIS: A total of 46 publications were selected for inclusion in this report, including 13 studies assessing genome-wide alterations, 18 studies assessing gene expression or microRNA expression profiles, three studies assessing proteomics, one study assessing genome-wide DNA methylation, and 14 studies evaluating distinct pathway alteration patterns. Differences between sporadic and hereditary UTUC, and between UTUC and BC, as well as molecular profiles associated with exposure to aristolochic acid are highlighted. Molecular pathways relevant to UTUC biology, such as alterations in FGFR3, TP53, or microsatellite instability, are discussed. Our findings are limited by tumor and patient heterogeneity and different platforms used in the studies. CONCLUSIONS: Molecular events in UTUC and BC can be shared or distinct. Consequently, molecular subtypes differ according to location. Further work is needed to define the epigenomic and proteomic features of UTUC, and understand the mechanisms by which they shape the clinical behavior of UTUC. PATIENT SUMMARY: We report the current data on the molecular alterations specific to upper tract urothelial carcinoma (UTUC), resulting from novel genomic and proteomic technologies. Although UTUC biology is comparable with that of bladder cancer, the rates and UTUC-enriched alterations support its uniqueness and the need for precision medicine strategies for this rare tumor type.
Academic Urology Unit University of Sheffield Sheffield UK
Department of Cell and Developmental Biology Weill Cornell Medicine New York NY USA
Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic
Department of Urology Icahn School of Medicine at Mount Sinai New York NY USA
Department of Urology Medical University of Vienna Vienna Austria
Department of Urology The University of Texas MD Anderson Cancer Center Houston TX USA
Department of Urology University of Texas Southwestern Medical Center Dallas TX USA
Department of Urology Weill Cornell Medical College New York Presbyterian Hospital New York NY USA
Englander Institute for Precision Medicine Weill Cornell Medicine New York NY USA
European Association of Urology research foundation Arnhem Netherlands
Institute of Pathology Friedrich Alexander Universität Erlangen Germany
Karl Landsteiner Institute of Urology and Andrology Vienna Austria
Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine New York NY USA
Section of Cancer Surveillance International Agency for Research on Cancer Lyon France
Urology GRC n°5 Predictive Onco Uro AP HP Hôpital Pitié Salpêtrière Sorbonne University Paris France
References provided by Crossref.org
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- $a CONTEXT: While upper tract urothelial carcinoma (UTUC) share histological appearance with bladder cancer (BC), the former has differences in etiology and clinical phenotype consistent with characteristic molecular alterations. OBJECTIVE: To systematically evaluate current genomic sequencing and proteomic data examining molecular alterations in UTUC. EVIDENCE ACQUISITION: A systematic review using PubMed, Scopus, and Web of Science was performed in December 2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. EVIDENCE SYNTHESIS: A total of 46 publications were selected for inclusion in this report, including 13 studies assessing genome-wide alterations, 18 studies assessing gene expression or microRNA expression profiles, three studies assessing proteomics, one study assessing genome-wide DNA methylation, and 14 studies evaluating distinct pathway alteration patterns. Differences between sporadic and hereditary UTUC, and between UTUC and BC, as well as molecular profiles associated with exposure to aristolochic acid are highlighted. Molecular pathways relevant to UTUC biology, such as alterations in FGFR3, TP53, or microsatellite instability, are discussed. Our findings are limited by tumor and patient heterogeneity and different platforms used in the studies. CONCLUSIONS: Molecular events in UTUC and BC can be shared or distinct. Consequently, molecular subtypes differ according to location. Further work is needed to define the epigenomic and proteomic features of UTUC, and understand the mechanisms by which they shape the clinical behavior of UTUC. PATIENT SUMMARY: We report the current data on the molecular alterations specific to upper tract urothelial carcinoma (UTUC), resulting from novel genomic and proteomic technologies. Although UTUC biology is comparable with that of bladder cancer, the rates and UTUC-enriched alterations support its uniqueness and the need for precision medicine strategies for this rare tumor type.
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