BRAF alterations are frequent in cerebellar low-grade astrocytomas with diffuse growth pattern

J Neuropathol Exp Neurol. 2012 Jul;71(7):631-9. doi: 10.1097/NEN.0b013e31825c448a.

Abstract

Cerebellar low-grade astrocytomas with a diffuse pattern of growth are uncommon, comprising World Health Organization (WHO) grade II diffuse astrocytomas (DA) and a minority of WHO grade I pilocytic astrocytomas (PA), so-called PA, "diffuse variant." Among 106 cerebellar low-grade astrocytomas (WHO grade I and II) operated on at the Mayo Clinic (1984-2010), we identified 19 such cases: 8 PA, "diffuse variant," 5 DA, and 6 that we were unable to classify further (low-grade astrocytomas, subtype indeterminate). We characterized these tumors using immunohistochemistry and currently available molecular markers (IDH1/2 mutations and BRAF mutation/fusion gene status) and investigated whether the markers could be used to aid the diagnostic process in combination with the clinical and pathologic features. KIAA1549-BRAF fusion was detected in 4 PA, "diffuse variant," 2 DA, and 2 low-grade astrocytomas, subtype indeterminate, indicating that these tumors were molecularly consistent with PA, the most common subtype of the series. A BRAF V600E mutation was detected in 1 PA, "diffuse variant" case; an IDH1 R132G mutation was found in 1 DA case. These results suggest that KIAA1549-BRAF fusion status and IDH1/2 and BRAF V600E mutational analyses may assist in the histologic classification of this diagnostically challenging group of tumors and result in a more accurate and objective combined molecular and histologic classification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Astrocytoma / genetics
  • Astrocytoma / metabolism*
  • Astrocytoma / pathology
  • Cerebellar Neoplasms / genetics
  • Cerebellar Neoplasms / metabolism*
  • Cerebellar Neoplasms / pathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism
  • Male
  • Middle Aged
  • Mutation / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism*
  • Retrospective Studies
  • Young Adult

Substances

  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf