title: Radiogenomics of clear cell renal cell carcinoma: associations between CT imaging features and mutations.
abstract: OBJECTIVE
  To investigate associations between computed tomographic (CT) features of clear cell renal cell carcinoma (RCC) and mutations in VHL, PBRM1, SETD2, KDM5C, or BAP1 genes.
  
  
  METHODS
  The institutional review board approved this retrospective, hypothesis-generating study of 233 patients with clear cell RCC and waived the informed consent requirement. The study was HIPAA compliant. Three radiologists independently reviewed pretreatment CT images of all clear cell RCCs without knowledge of their genomic profile. One radiologist measured largest diameter and enhancement parameters of each clear cell RCC. Associations between CT features and mutations in VHL, PBRM1, SETD2, KDM5C, and BAP1 genes were tested by using the Fisher exact test. Associations between mutations and size and enhancement were assessed by using the independent t test. Interreader agreement was calculated by using the Fleiss κ.
  
  
  RESULTS
  Mutation frequencies among clear cell RCCs were as follows: VHL, 53.2% (124 of 233); PBRM1, 28.8% (67 of 233); SETD2, 7.3% (17 of 233); KDM5C, 6.9% (16 of 233); and BAP1, 6.0% (14 of 233). Mutations of VHL were significantly associated with well-defined tumor margins (P = .013), nodular tumor enhancement (P = .021), and gross appearance of intratumoral vascularity (P = .018). Mutations of KDM5C and BAP1 were significantly associated with evidence of renal vein invasion (P = .022 and .046, respectively). The genotype of solid clear cell RCC differed significantly from the genotype of multicystic clear cell RCC. While mutations of SETD2, KDM5C, and BAP1 were absent in multicystic clear cell RCC, mutations of VHL (P = .016) and PBRM1 (P = .017) were significantly more common among solid clear cell RCC. Interreader agreement for CT feature assessments ranged from substantial to excellent (κ = 0.791-0.912).
  
  
  CONCLUSIONS
  This preliminary radiogenomics analysis of clear cell RCC revealed associations between CT features and underlying mutations that warrant further investigation and validation.
authors.affiliation: From the Genitourinary Imaging Group, Department of Radiology (C.A.K., P.L.D.P., J.C., H.H., O.A.), Urology Service, Department of Surgery (A.A.H., P.R.), Human Oncology & Pathogenesis Program (A.A.H., J.J.H.), Department of Epidemiology and Biostatistics (I.O.), and Department of Medicine, Genitourinary Oncology Service (R.M., J.J.H.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Radiology Academic Offices, Room C278, New York, NY 10065.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Karlo
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Di Paolo
authors.forename: Joshua
authors.initials: J
authors.lastname: Chaim
authors.forename: A Ari
authors.initials: AA
authors.lastname: Hakimi
authors.forename: Irina
authors.initials: I
authors.lastname: Ostrovnaya
authors.forename: Paul
authors.initials: P
authors.lastname: Russo
authors.forename: Hedvig
authors.initials: H
authors.lastname: Hricak
authors.forename: Robert
authors.initials: R
authors.lastname: Motzer
authors.forename: James J
authors.initials: JJ
authors.lastname: Hsieh
authors.forename: Oguz
authors.initials: O
authors.lastname: Akin
mesh_terms: D000328:Adult; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000235:genetics*; D003287:Contrast Media; D004268:DNA-Binding Proteins; D005260:Female; D005838:Genotype; D056466:Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics*; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
chemical_list: C400134:BAP1 protein, human; D003287:Contrast Media; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C102195:PBRM1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D056466:Histone Demethylases; C086877:KDM5C protein, human; D010089:Oxidoreductases, N-Demethylating; D011495:Histone-Lysine N-Methyltransferase; C521636:SETD2 protein, human; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D043222:Ubiquitin Thiolesterase; C497446:VHL protein, human
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