TY - JOUR
T1 - Molecular Characterization of Upper Tract Urothelial Carcinoma in the Era of Next-generation Sequencing
T2 - A Systematic Review of the Current Literature
AU - Hassler, Melanie R.
AU - Bray, Freddie
AU - Catto, James W.F.
AU - Grollman, Arthur P.
AU - Hartmann, Arndt
AU - Margulis, Vitaly
AU - Matin, Surena F.
AU - Roupret, Morgan
AU - Sfakianos, John P.
AU - Shariat, Shahrokh F.
AU - Faltas, Bishoy M.
N1 - Funding Information:
Financial disclosures: Shahrokh F. Shariat certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: James W.F. Catto: reimbursement for consultancy from Astra Zeneca, Roche, and Janssen; speaker fees from BMS, MSD, Nucleix, and Roche; and honoraria for membership of an advisory board from Ferring and Janssen. Arndt Hartmann: honoraria for lectures from or consulting/advisory boards for Abbvie, AstraZeneca, Biontech, BMS, Boehringer Ingelheim, Cepheid, Diaceutics, Illumina, Ipsen, Janssen, MSD, Nanostring, Novartis, Qiagen, QUIP GmbH, Roche, and 3DHistotech, and other research support from AstraZeneca, Biontech, Cepheid, Illumina, Janssen, Nanostring, Qiagen, QUIP GmbH, and Roche. Surena F. Matin: consultant for Taris Bio. Morgan Roupret: grants/research support from GSK, Pfizer, and Roche; honoraria or consultation fees from Lilly, GSK, Ipsen, Astellas, Takeda, Sanofi Pasteur, and Medac. Shahrokh F. Shariat: honoraria for lectures from or consulting/advisory boards for Astellas, Astra Zeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Janssen, Lilly, MSD, Olympus, Pfizer, Pierre Fabre, Richard Wolf, Roche, Sanochemia, Sanofi, Takeda, and Urogen; patents: Method to determine prognosis after therapy for prostate cancer (granted 2002-09-06), Methods to determine prognosis after therapy for bladder cancer (granted 2003-06-19), Prognostic methods for patients with prostatic disease (granted 2004-08-05), and Soluble Fas urinary marker for the detection of bladder transitional cell carcinoma (granted 2010-07-20). Bishoy M. Faltas: supported by the Department of Defense CDMRP Career Development Award (grant CA160212), Urotoday (honoraria), Lilly ( research support), and Immunomedics (advisory board).
Publisher Copyright:
© 2020
PY - 2020/8
Y1 - 2020/8
N2 - 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. Recent data obtained by high-throughput molecular profiling technologies underscore the distinct molecular alterations found in upper tract urothelial carcinoma (UTUC). UTUC biology shares many features with bladder cancer, but there are important specific distinctions that support the need for UTUC-targeted therapeutic strategies.
AB - 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. Recent data obtained by high-throughput molecular profiling technologies underscore the distinct molecular alterations found in upper tract urothelial carcinoma (UTUC). UTUC biology shares many features with bladder cancer, but there are important specific distinctions that support the need for UTUC-targeted therapeutic strategies.
KW - Genomics
KW - Molecular alterations
KW - Molecular characterization
KW - Next-generation sequencing
KW - Proteomics
KW - RNAseq
KW - Renal pelvis
KW - Transcriptomics
KW - Ureter
KW - Urothelial carcinoma
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U2 - 10.1016/j.eururo.2020.05.039
DO - 10.1016/j.eururo.2020.05.039
M3 - Review article
C2 - 32571725
AN - SCOPUS:85086733082
VL - 78
SP - 209
EP - 220
JO - European Urology
JF - European Urology
SN - 0302-2838
IS - 2
ER -