Mutation profiling of pleomorphic xanthoastrocytoma and giant cell glioblastoma arising in a PXA reveals BRAF V600E mutations.

<p>The sections on the left illustrate SNaPshot genotyping and the sections on the right depict Sanger sequencing of <i>BRAF</i> exon 15 for the same samples. The top panel shows genotyping data obtained with normal male genomic DNA (Promega, Madison, WI). The lower panels illustrate BRAF V600E (c.1799T>A) mutation detection (arrows) in tumor DNA derived from formalin-fixed paraffin-embedded specimens of representative examples of: PXA (BT21), anaplastic PXA (BT22) and gcGBM arising in a PXA (BT49). Assays: (1) <i>EGFR</i> 2235_49del R; (2) <i>NRAS</i> 38; (3) <i>BRAF</i> 1799; (4) <i>NRAS</i> 182; (5) <i>PIK3CA</i> 263; (6) <i>TP53</i> 742; (7) <i>CTNNB1</i> 95 and (8) <i>CTNNB1</i> 122.</p

Representative photomicrographs of tumors.

<p>A. H&E-stained section of a pleomorphic xanthoastrocytoma (PXA, BT06) demonstrating fascicular growth pattern and prominent intercellular reticulin deposition (B) corresponding to PXA (m). C. H&E-stained section of PXA (BT21) that demonstrates neither a fascicular growth pattern nor prominent intercellular reticulin deposition (D). E. H&E-stained section of a giant cell glioblastoma (gcGBM) arising from a PXA (BT49) with marked pleomorphism and giant cells and multifocal reticulin deposition (F).</p

Clinical Data and Summary of Results.

<p>PXA – pleomorphic xanthoastrocytoma; PXA (m) – pleomorphic xanthoastrocytoma with mesenchymal-like growth pattern; aPXA – anaplastic pleomorphic xanthoastrocytoma; NA – Not assessed.</p

Mutation analysis of GBM.

<p>SNaPshot clinical genotyping of 62 glioblastoma cases from MGH identified cancer gene mutations that confer a favorable prognosis to the patients (IDH1) or that activate pathways targeted by therapeutic agents under clinical development (BRAF, KRAS and PIK3CA).</p