Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma
- 1.4k Downloads
Separation of pilocytic astrocytoma from diffuse astrocytomas frequently poses problems mostly related to small sample size. Precise classification and grading are essential due to different therapeutic strategies prompted by diagnoses of pilocytic astrocytoma WHO grade I, diffuse astrocytomas WHO grade II or anaplastic astrocytoma WHO grade III. Recently, genomic aberrations with a high specificity for distinct glioma entities have been described. Pilocytic astrocytomas carry a duplication at chromosome band 7q34 containing a BRAF–KIAA1549 gene fusion in the majority of cases. IDH1 mutations are observed very frequently in adult astrocytomas and IDH2 mutations have been reported in some astrocytomas. We examined a series of 120 astrocytomas including 70 pilocytic astrocytomas WHO grade I and 50 diffuse astrocytomas WHO grade II for both, BRAF–KIAA1549 fusion with a newly developed FISH assay and mutations in IDH1 and IDH2 by direct sequencing. Pilocytic astrocytomas contained the BRAF fusion in 49 cases (70%) but neither IDH1 nor IDH2 mutations. Astrocytomas WHO grade II exhibited IDH1 mutations in 38 cases (76%) but neither IDH2 mutations nor BRAF fusions. Thus, combined molecular analysis of BRAF and IDH1 is a sensitive and highly specific approach to separate pilocytic astrocytoma from diffuse astrocytoma.
KeywordsBRAF IDH1 IDH2 Pilocytic astrocytoma Diffuse astrocytoma
We wish to thank F. Mößler, K. Lindenberg, A. Wittman and B. Walter for skillful technical assistance. This work was supported by the Bundesministerium für Bildung und Forschung (BMBF–01ES0730) to AvD and CH and by a grant from the “Tour der Hoffnung” to SP.
- 6.Ichimura K, Pearson DM, Kocialkowski S et al (2009) IDH1 mutations are present in the majority of common adult gliomas but are rare in primary glioblastomas. Neuro Oncol (epub ahead of print)Google Scholar
- 8.Jones DT, Kocialkowski S, Liu L et al (2009) Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549:BRAF fusion in activating the MAPK pathway in pilocytic astrocytoma. Oncogene (epub ahead of print)Google Scholar
- 9.Kruchko C, Brem S, Lee H et al (2008) Statistical report: primary brain tumors in the United States, 2000–2004, Hinsdale: Central Brain Tumor Registry of the United States (CBTRUS)Google Scholar
- 11.Louis DN et al (2007) WHO classification of tumours of the central nervous system, 4th edn. World Health Organization classification of tumours. International Agency for Research on Cancer, LyonGoogle Scholar
- 15.Sievert AJ, Jackson EM, Gai X et al (2009) Duplication of 7q34 in pediatric low-grade astrocytomas detected by high-density single-nucleotide polymorphism-based genotype arrays results in a novel BRAF fusion gene. Brain Pathol (epub ahead of print)Google Scholar