title: Race disparities in peptide profiles of North American and Kenyan Wilms tumor specimens.
abstract: BACKGROUND
  Wilms tumor (WT) is the most common childhood kidney cancer worldwide and arises in children of black African ancestry with greater frequency and severity than other race groups. A biologic basis for this pediatric cancer disparity has not been previously determined. We hypothesized that unique molecular fingerprints might underlie the variable incidence and distinct disease characteristics of WT observed between race groups.
  
  
  METHODS
  To evaluate molecular disparities between WTs of different race groups, the Children's Oncology Group provided 80 favorable histology specimens divided evenly between black and white patients and matched for disease characteristics. As a surrogate of black sub-Saharan African patients, we also analyzed 18 Kenyan WT specimens. Tissues were probed for peptide profiles using matrix-assisted laser desorption ionization time of flight imaging mass spectrometry. To control for histologic variability within and between specimens, cellular regions were analyzed separately as triphasic (containing blastema, epithelia, and stroma), blastema only, and stroma only. Data were queried using ClinProTools and statistically analyzed.
  
  
  RESULTS
  Peptide profiles, detected in triphasic WT regions, recognized race with good accuracy, which increased for blastema- or stroma-only regions. Peptide profiles from North American WTs differed between black and white race groups but were far more similar in composition than Kenyan specimens. Individual peptides were identified that also associated with WT patient and disease characteristics (eg, treatment failure and stage). Statistically significant peptide fragments were used to sequence proteins, revealing specific cellular signaling pathways and candidate drug targets.
  
  
  CONCLUSIONS
  Wilms tumor specimens arising among different race groups show unique molecular fingerprints that could explain disparate incidences and biologic behavior and that could reveal novel therapeutic targets.
authors.affiliation: Division of Pediatric Hematology and Oncology, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Libes
authors.affiliation: Department of Biochemistry, Mass Spectrometry Research Center, Tissue Core, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Erin H
authors.initials: EH
authors.lastname: Seeley
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Axt
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Janene
authors.initials: J
authors.lastname: Pierce
authors.affiliation: Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Hernan
authors.initials: H
authors.lastname: Correa
authors.affiliation: Division of Pediatric Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN; Kijabe Mission Hospital, Kenya.
authors.forename: Mark
authors.initials: M
authors.lastname: Newton
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University School of Medicine, Nashville, TN; Kijabe Mission Hospital, Kenya.
authors.forename: Erik
authors.initials: E
authors.lastname: Hansen
authors.affiliation: Department of Biochemistry, Mass Spectrometry Research Center, Tissue Core, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Audra
authors.initials: A
authors.lastname: Judd
authors.affiliation: Proteomics Laboratory, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Hayes
authors.initials: H
authors.lastname: McDonald
authors.affiliation: Department of Biochemistry, Mass Spectrometry Research Center, Tissue Core, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Caprioli
authors.affiliation: Children's Oncology Group Statistics and Data Center, Department of Biostatistics, University of Florida, Gainseville, FL.
authors.forename: Arlene
authors.initials: A
authors.lastname: Naranjo
authors.affiliation: Children's Oncology Group Statistics and Data Center, Department of Biostatistics, University of Florida, Gainseville, FL.
authors.forename: Vicki
authors.initials: V
authors.lastname: Huff
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University School of Medicine, Nashville, TN; Kijabe Mission Hospital, Kenya.
authors.forename: James A
authors.initials: JA
authors.lastname: O'Neill
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University School of Medicine, Nashville, TN. Electronic address: harold.lovvorn@vanderbilt.edu.
authors.forename: Harold N
authors.initials: HN
authors.lastname: Lovvorn
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism*; D044383:Black People; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005260:Female; D054624:Health Status Disparities; D006801:Humans; D007630:Kenya; D007680:Kidney Neoplasms / Q000208:ethnology* / Q000378:metabolism; D008297:Male; D025341:Principal Component Analysis; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014481:United States; D044465:White People; D009396:Wilms Tumor / Q000208:ethnology* / Q000378:metabolism; D001741:Black or African American
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome