title: BRAF exon 15 mutations in pediatric renal stromal tumors: prevalence in metanephric stromal tumors.
abstract: Metanephric stromal tumors (MSTs) are rare renal stromal tumors that predominantly affect children. They belong to the metanephric family of tumors, along with metanephric adenofibroma and metanephric adenoma. The previous documentation of BRAF exon 15 mutations in 88% of metanephric adenomas and in isolated cases of metanephric adenofibroma prompted us to investigate the prevalence of these mutations in MSTs and in other pediatric renal stromal tumors. In this study, 17 MSTs, 22 congenital mesoblastic nephromas, and 6 ossifying renal tumors of infancy were selected for BRAF exon 15 testing. Tumor genomic DNA was extracted from formalin-fixed paraffin-embedded tissue, followed by polymerase chain reaction amplification and Sanger dideoxy sequencing with primers flanking the BRAF exon 15 gene. BRAF exon 15 mutations were found in 11 (65%) of the 17 cases of MST, all corresponding to a thymidine-to-adenine substitution at codon 600 (BRAF V600E). All other renal stromal tumors tested were negative for BRAF exon 15 mutations. In conclusion, BRAF V600E mutations are encountered in most MSTs, supporting a link with other metanephric tumors and suggesting a clonal event possibly affecting primordial renal cells. In addition, BRAF V600E mutations have been associated with oncogene-induced senescence in other benign tumors, providing clues to the pathogenesis of metanephric neoplasms in keeping with their overall benign behavior. Our results also suggest a potential diagnostic use for BRAF exon 15 mutations in differentiating MSTs from other pediatric renal stromal tumors, particularly in limited samples.
authors: Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL - 60611.
authors: Lily
authors: L
authors: Marsden
authors: Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL - 60611.
authors: Lawrence J
authors: LJ
authors: Jennings
authors: Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL - 60611.
authors: Samantha
authors: S
authors: Gadd
authors: Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL - 60611.
authors: Min
authors: M
authors: Yu
authors: Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL - 60611.
authors: Elizabeth J
authors: EJ
authors: Perlman
authors: Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL - 60611. Electronic address: mcajaiba@luriechildrens.org.
authors: Mariana M
authors: MM
authors: Cajaiba
mesh_terms: D000367:Age Factors; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D018201:Nephroma, Mesoblastic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF gene; Congenital mesoblastic nephroma; Metanephric stromal tumor; Ossifying renal tumor of infancy; Pediatric renal tumors