title: Genomic Copy Number Alterations in Renal Cell Carcinoma with Sarcomatoid Features.
abstract: Sarcomatoid changes in renal cell carcinoma are associated with a poor prognosis. The identification of genetic alterations that drive this aggressive phenotype could aid in the development of more effective targeted therapies. In this study we aimed to pinpoint unique copy number alterations in sarcomatoid renal cell carcinoma compared to classical renal cell carcinoma subtypes.
  
  
  
  Genomic copy number analysis was performed using single nucleotide polymorphism based microarrays on tissue extracted from the tumors of 81 patients who underwent renal mass excision, including 17 with sarcomatoid renal cell carcinoma.
  
  
  
  Sarcomatoid renal cell carcinoma showed a significantly higher number of copy number alterations than clear cell, papillary and chromophobe renal cell carcinoma (mean 18.0 vs 5.8, 6.5 and 7.2, respectively, p <0.0001). Copy number losses of chromosome arms 9q, 15q, 18p/q and 22q, and gains of 1q and 8q occurred in a significantly higher proportion of sarcomatoid renal cell carcinomas than in the other 3 histologies. Patients with sarcomatoid renal cell carcinoma demonstrated significantly worse overall survival compared to those without that condition on Kaplan-Meier analysis (p = 0.0001). Patients with 9 or more copy number alterations also demonstrated significantly worse overall survival than those with fewer than 9 copy number alterations (p = 0.004).
  
  
  
  Sarcomatoid changes in renal cell carcinoma are associated with a high rate of chromosomal imbalances with losses of 9q, 15q, 18p/q and 22q, and gains of 1q and 8q occurring at significantly higher frequencies in comparison to nonsarcomatoid renal cell carcinoma. Identifying candidate driver genes or tumor suppressor loci in these chromosomal regions may help identify targets for future therapies.
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Timothy
authors.initials: T
authors.lastname: Ito
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Jianming
authors.initials: J
authors.lastname: Pei
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Essel
authors.initials: E
authors.lastname: Dulaimi
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Craig
authors.initials: C
authors.lastname: Menges
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Abbosh
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Smaldone
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: David Y T
authors.initials: DY
authors.lastname: Chen
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Greenberg
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kutikov
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Viterbo
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Uzzo
authors.affiliation: Cancer Biology Program and Blood Cell Development and Function Program (ED), Fox Chase Cancer Center, Philadelphia, Pennsylvania. Electronic address: Joseph.Testa@fccc.edu.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Testa
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality; D056915:DNA Copy Number Variations; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods
keywords: carcinoma, renal cell; chromosome aberrations; kidney; microarray analysis; polymorphism, single nucleotide