title: Alternate Metabolic Programs Define Regional Variation of Relevant Biological Features in Renal Cell Carcinoma Progression.
abstract: Clear cell renal cell carcinoma (ccRCC) has recently been redefined as a highly heterogeneous disease. In addition to genetic heterogeneity, the tumor displays risk variability for developing metastatic disease, therefore underscoring the urgent need for tissue-based prognostic strategies applicable to the clinical setting. We have recently employed the novel PET/magnetic resonance (MR) image modality to enrich our understanding of how tumor heterogeneity can relate to gene expression and tumor biology to assist in defining individualized treatment plans.
  
  
  
  ccRCC patients underwent PET/MR imaging, and these images subsequently used to identify areas of varied intensity for sampling. Samples from 8 patients were subjected to histologic, immunohistochemical, and microarray analysis.
  
  
  
  Tumor subsamples displayed a range of heterogeneity for common features of hypoxia-inducible factor expression and microvessel density, as well as for features closely linked to metabolic processes, such as GLUT1 and FBP1. In addition, gene signatures linked with disease risk (ccA and ccB) also demonstrated variable heterogeneity, with most tumors displaying a dominant panel of features across the sampled regions. Intriguingly, the ccA- and ccB-classified samples corresponded with metabolic features and functional imaging levels. These correlations further linked a variety of metabolic pathways (i.e., the pentose phosphate and mTOR pathways) with the more aggressive, and glucose avid ccB subtype.
  
  
  
  Higher tumor dependency on exogenous glucose accompanies the development of features associated with the poor risk ccB subgroup. Linking these panels of features may provide the opportunity to create functional maps to enable enhanced visualization of the heterogeneous biologic processes of an individual's disease. Clin Cancer Res; 22(12); 2950-9. ©2016 AACR.
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina. Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Samira A
authors.initials: SA
authors.lastname: Brooks
authors.affiliation: Department of Radiology, University of North Carolina, Chapel Hill, North Carolina. Department of Radiology, Nuclear Medicine, University of North Carolina at Chapel Hill, North Carolina. kimryn.rathmell@vanderbilt.edu khandani@med.unc.edu.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Khandani
authors.affiliation: Department of Radiology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Julia R
authors.initials: JR
authors.lastname: Fielding
authors.affiliation: Department of Radiology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Weili
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Sills
authors.affiliation: Department of Radiology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Yueh
authors.initials: Y
authors.lastname: Lee
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Arreola
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina. Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Mathew I
authors.initials: MI
authors.lastname: Milowsky
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina. Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wallen
authors.affiliation: Department of Radiology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Woods
authors.affiliation: Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Angie B
authors.initials: AB
authors.lastname: Smith
authors.affiliation: Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Mathew E
authors.initials: ME
authors.lastname: Nielsen
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: Department of Radiology, Nuclear Medicine, University of North Carolina at Chapel Hill, North Carolina. Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, Raleigh, North Carolina.
authors.forename: David S
authors.initials: DS
authors.lastname: Lalush
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina. Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. kimryn.rathmell@vanderbilt.edu khandani@med.unc.edu.
authors.forename: W Kimryn
authors.initials: WK
authors.lastname: Rathmell
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D046228:Microarray Analysis; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor