title: Analysis of molecular cytogenetic changes in metastatic renal cell carcinoma in the setting of everolimus treatment: a pilot project.
abstract: BACKGROUND
  The mTOR inhibitors have improved outcomes for patients with metastatic renal cell carcinoma (mRCC) but the duration of benefit is variable. Currently there are no predictive biomarkers for preselecting patients who are more likely to benefit from these agents. We undertook an exploratory translational study evaluating molecular cytogenetic changes in the context of outcomes from treatment with everolimus.
  
  
  METHODS
  Ten patients with clear cell mRCC treated with everolimus were enrolled. Pretreatment tissue specimens were analyzed for molecular cytogenetic changes using fluorescence in situ hybridization and progression-free survival (PFS) data were obtained. Gene probes chosen for this analysis were: Von Hippel Lindau, fragile histidine triad, fibroblast growth factor receptor (FGFR) 1, FGFR3, PDGFβ, PDGFRβ, epidermal growth factor receptor, and myelocytomatosis viral oncogene.
  
  
  RESULTS
  Median PFS was 8.75 months. Two patients with the longest PFS (28 months and 23 months) had gain of PDGFβ and PDGFRβ. This was also observed in 3 other patients who had a PFS of 11.5 months, 8 months, and 5.5 months, respectively. Cytogenetic evolution was observed between primary and metastatic specimens.
  
  
  CONCLUSIONS
  PDGFβ and PDGFRβ gene status might be of relevance to everolimus therapy. Further research evaluating the utility of these potential biomarkers is required.
authors: Adult Oncology Research Centre, Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand.
authors: Imogen R
authors: IR
authors: Caldwell
authors: IGENZ Ltd, Auckland, New Zealand.
authors: Paul
authors: P
authors: Oei
authors: IGENZ Ltd, Auckland, New Zealand.
authors: Daniel
authors: D
authors: Ng
authors: Adult Oncology Research Centre, Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand.
authors: Beth
authors: B
authors: Caudwell
authors: Adult Oncology Research Centre, Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand.
authors: Peter C C
authors: PC
authors: Fong
authors: Adult Oncology Research Centre, Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand. Electronic address: ReubenB@adhb.govt.nz.
authors: Reuben J
authors: RJ
authors: Broom
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D000068338:Everolimus; D020797:Receptor, Platelet-Derived Growth Factor beta; D020123:Sirolimus
keywords: Biomarkers; Mammalian target of rapamycin inhibitor; PDGFRβ; PDGFβ; mTOR inhibitor