title: Genomic Biomarkers for the Prediction of Stage and Prognosis of Upper Tract Urothelial Carcinoma.
abstract: Genomic characterization of radical nephroureterectomy specimens in patients with upper tract urothelial carcinoma may allow for thoughtful integration of systemic and targeted therapies. We sought to determine whether genomic alterations in upper tract urothelial carcinoma are associated with adverse pathological and clinical outcomes.
  
  
  
  Next generation exon capture sequencing of 300 cancer associated genes was performed in 83 patients with upper tract urothelial carcinoma. Genomic alterations were assessed individually and also grouped into core signal transduction pathways or canonical cell functions for association with clinicopathological outcomes. Binary outcomes, including grade (high vs low), T stage (pTa/T1/T2 vs pT3/T4) and organ confined status (pT2 or less and N0/Nx vs greater than pT2 or N+) were assessed with the Kruskal-Wallis and Fisher exact tests as appropriate. Associations between alterations and survival were estimated using the Kaplan-Meier method and Cox regression.
  
  
  
  Of the 24 most commonly altered genes in 9 pathways TP53/MDM2 alterations and FGFR3 mutations were the only 2 alterations uniformly associated with high grade, advanced stage, nonorgan confined disease, and recurrence-free and cancer specific survival. TP53/MDM2 alterations were associated with adverse clinicopathological outcomes whereas FGFR3 mutations were associated with favorable outcomes. We created a risk score using TP53/MDM2 and FGFR3 status that was able to discriminate between adverse pathological and clinical outcomes, including in the subset of patients with high grade disease. The study is limited by small numbers and lack of validation.
  
  
  
  Our data indicate that specific genomic alterations in radical nephroureterectomy specimens correlate with tumor grade, stage and cancer specific survival outcomes.
authors.affiliation: Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bagrodia
authors.affiliation: Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY.|Weill Medical College of Cornell University, New York, NY.
authors.forename: Eugene K
authors.initials: EK
authors.lastname: Cha
authors.affiliation: Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: John P
authors.initials: JP
authors.lastname: Sfakianos
authors.affiliation: Department of Epidemiology and Biostatistics; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Zabor
authors.affiliation: Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY.|Weill Medical College of Cornell University, New York, NY.
authors.forename: Bernard H
authors.initials: BH
authors.lastname: Bochner
authors.affiliation: Department of Pathology; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Hikmat A
authors.initials: HA
authors.lastname: Al-Ahmadie
authors.affiliation: Weill Medical College of Cornell University, New York, NY.|Department of Medicine, Genitourinary Oncology Service; Memorial Sloan Kettering Cancer Center, New York, NY.|Human Oncology & Pathogenesis Program; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: David B
authors.initials: DB
authors.lastname: Solit
authors.affiliation: Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY.|Weill Medical College of Cornell University, New York, NY.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Coleman
authors.affiliation: Weill Medical College of Cornell University, New York, NY.|Department of Medicine, Genitourinary Oncology Service; Memorial Sloan Kettering Cancer Center, New York, NY.|Human Oncology & Pathogenesis Program; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Gopa
authors.initials: G
authors.lastname: Iyer
authors.affiliation: Human Oncology & Pathogenesis Program; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Sasinya N
authors.initials: SN
authors.lastname: Scott
authors.affiliation: Human Oncology & Pathogenesis Program; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Ronak
authors.initials: R
authors.lastname: Shah
authors.affiliation: Department of Epidemiology and Biostatistics; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Irina
authors.initials: I
authors.lastname: Ostrovnaya
authors.affiliation: Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Byron
authors.initials: B
authors.lastname: Lee
authors.affiliation: Human Oncology & Pathogenesis Program; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Neil B
authors.initials: NB
authors.lastname: Desai
authors.affiliation: Department of Pathology; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Qinghu
authors.initials: Q
authors.lastname: Ren
authors.affiliation: Weill Medical College of Cornell University, New York, NY.|Department of Medicine, Genitourinary Oncology Service; Memorial Sloan Kettering Cancer Center, New York, NY.|Human Oncology & Pathogenesis Program; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Rosenberg
authors.affiliation: Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY.|Weill Medical College of Cornell University, New York, NY.
authors.forename: Guido
authors.initials: G
authors.lastname: Dalbagni
authors.affiliation: Weill Medical College of Cornell University, New York, NY.|Department of Medicine, Genitourinary Oncology Service; Memorial Sloan Kettering Cancer Center, New York, NY.|Human Oncology & Pathogenesis Program; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Bajorin
authors.affiliation: Department of Pathology; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.affiliation: Department of Pathology; Memorial Sloan Kettering Cancer Center, New York, NY.|Human Oncology & Pathogenesis Program; Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Berger
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D000074682:Nephroureterectomy; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods; D016019:Survival Analysis; D014513:Ureter / Q000473:pathology / Q000601:surgery; D014571:Urologic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: biological markers; carcinoma; genomics; kidney; ureter