BRAF alterations are frequent in cerebellar low-grade astrocytomas with diffuse growth pattern.
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.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Cristiane M
CM
Ida
Sally R
SR
Lambert
Fausto J
FJ
Rodriguez
Jesse S
JS
Voss
Brooke E
BE
Mc Cann
Amber R
AR
Seys
Kevin C
KC
Halling
V Peter
VP
Collins
Caterina
C
Giannini
D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D055815:Young Adult
C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf