title: Renal medullary carcinoma: molecular, pathological and clinical evidence for treatment with topoisomerase-inhibiting therapy.
abstract: METHODS
  Aetiology (case series) Level of Evidence 4.
  
  
  OBJECTIVE
  To present the molecular rationale and potential clinical benefit of topoisomerase II (TopoII)-inhibiting therapy for renal medullary carcinoma (RMC), a rare but extremely lethal form of kidney cancer that classically afflicts young men with sickle-cell trait. The current therapeutic approach with these aggressive tumours is radical nephrectomy followed by systemic chemotherapy, but the prognosis remains dismal.
  
  
  METHODS
  The whole-genome expression was analysed in four RMC tumours. We also report a case of metastatic RMC in which a complete response was achieved for 9 months using a TopoII-inhibiting therapy.
  
  
  RESULTS
  Expanded whole-genome expression analysis showed increases of TopoII in all cases. There was also overall deregulation of DNA remodelling and repair, and an ontological association between RMC and urothelial carcinoma. Using a TopoII-inhibiting agent, there was a complete response for 9 months in a patient with metastatic RMC.
  
  
  CONCLUSIONS
  This report provides molecular evidence for the rational use of TopoII inhibitors in the treatment of RMC.
authors.affiliation: The James Buchanan Brady Urologic Institute, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA. eschaef4@jhmi.edu
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schaeffer
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Guzzo
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Furge
authors.forename: George
authors.initials: G
authors.lastname: Netto
authors.forename: Michael
authors.initials: M
authors.lastname: Westphal
authors.forename: Karl
authors.initials: K
authors.lastname: Dykema
authors.forename: Ximing
authors.initials: X
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.forename: Christian P
authors.initials: CP
authors.lastname: Pavlovich
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications*; D000951:Antigens, Neoplasm / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018276:Carcinoma, Medullary / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000628:therapy*; D003131:Combined Modality Therapy; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D008297:Male; D009392:Nephrectomy; D011379:Prognosis; D059005:Topoisomerase II Inhibitors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II