title: Gain of chromosome 8q is associated with metastases and poor survival of patients with clear cell renal cell carcinoma.
abstract: BACKGROUND
  The aim of this study was to evaluate the prevalence of chromosome 8q gain in clear cell renal cell carcinoma (CCRCC) and to correlate the findings with tumor phenotype and disease-specific survival (DSS).
  
  
  METHODS
  The tumor karyotypes of 336 consecutive patients with CCRCC were prospectively evaluated with classical cytogenetic analysis. Chromosome 8q status was correlated with clinicopathological variables, and its impact on DSS was evaluated.
  
  
  RESULTS
  Gain of 8q occurred in 28 tumors (8.3%). Gain of 8q was associated with a higher risk of regional lymph node (21.4% vs 6.2%, P = .011) and distant metastases (50.0% vs 24.4%, P = .006), and greater tumor sizes (P = .030). Patients with gain of 8q had a 3.22-fold increased risk of death from CCRCC (P < .001). In multivariable analysis, gain of 8q was identified as an independent prognostic factor (hazard ratio, 2.37; P = .006). The concordance index of a multivariable base model increased significantly following inclusion of 8q gain (P = .0015).
  
  
  CONCLUSIONS
  Gain of chromosome 8q occurs in a subset of CCRCCs and is associated with an increased risk of metastases and death from CCRCC. Because the proto-oncogene c-MYC is among the list of candidate genes located on 8q, our data suggest that these tumors may have unique pathways activated, which are associated with an aggressive tumor phenotype. If confirmed, defining tumors with gain of 8q may assist in identifying patients who would benefit for specific c-MYC inhibitors or agents that target the MAPK/ERK (mitogen-activated protein kinase) pathway.
authors.affiliation: Department of Urology, Institute of Urologic Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095-7384, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Klatte
authors.forename: Nils
authors.initials: N
authors.lastname: Kroeger
authors.forename: Edward N
authors.initials: EN
authors.lastname: Rampersaud
authors.forename: Frédéric D
authors.initials: FD
authors.lastname: Birkhäuser
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Logan
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Sonn
authors.forename: Joseph
authors.initials: J
authors.lastname: Riss
authors.forename: P Nagesh
authors.initials: PN
authors.lastname: Rao
authors.forename: Fairooz F
authors.initials: FF
authors.lastname: Kabbinavar
authors.forename: Arie S
authors.initials: AS
authors.lastname: Belldegrun
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Pantuck
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D002898:Chromosomes, Human, Pair 8; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005260:Female; D016259:Genes, myc; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D048049:Extracellular Signal-Regulated MAP Kinases