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Journal of Neuropathology & Experimental Neurology:
doi: 10.1097/NEN.0b013e31825c448a
Original Articles

BRAF Alterations Are Frequent in Cerebellar Low-Grade Astrocytomas With Diffuse Growth Pattern

Ida, Cristiane M. MD; Lambert, Sally R. MD; Rodriguez, Fausto J. MD; Voss, Jesse S. CT; Mc Cann, Brooke E. BS; Seys, Amber R. MS; Halling, Kevin C. MD, PhD; Collins, V. Peter MD; Giannini, Caterina MD, PhD

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Abstract

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.

© 2012 American Association of Neuropathologists, Inc

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