We provide the first comprehensive genome-wide genetic alternation profiling of GS, which suggests novel prognostic subgroups in GS patients based on their TP53 mutation status and provides new insight in the pathogenesis and targeted treatment of GS.
<b>Objective:</b> Gliosarcoma (GSC), a rare malignant brain tumor, is considered as a variant of isocitrate dehydrogenase 1 wild type (IDH1-WT) glioblastoma (GBM).
As mutations of the p53 tumor suppressor gene represent an early event in the development of gliomas, we attempted to determine whether both components of gliosarcomas share identical alterations of the p53 gene.
Single-strand conformation polymorphism followed by direct DNA sequencing revealed p53 mutations in five of 19 gliosarcomas (26%) and PTEN mutations in seven cases (37%).
We identified a subset of tumors (n = 18, 8.8% of high-grade gliomas) exhibiting moderate-to-strong immunoreactivity that enriched for the IDH-wild-type glioblastoma variants gliosarcoma (n = 10) and the newly described epithelioid glioblastoma (n = 4).
IDH1 and IDH2 mutations were absent in all 36 gliosarcomas and in 18 of 19 giant cell glioblastomas analyzed, indicating that they are histological variants of primary glioblastoma.
Single-strand conformation polymorphism followed by direct DNA sequencing revealed p53 mutations in five of 19 gliosarcomas (26%) and PTEN mutations in seven cases (37%).
We identified a subset of tumors (n = 18, 8.8% of high-grade gliomas) exhibiting moderate-to-strong immunoreactivity that enriched for the IDH-wild-type glioblastoma variants gliosarcoma (n = 10) and the newly described epithelioid glioblastoma (n = 4).
We demonstrate that gliosarcoma bears somatic alterations in gene coding for PI3K/Akt (<i>PTEN</i>, <i>PI3K</i>) and RAS/MAPK (<i>NF1</i>, <i>BRAF</i>) signaling pathways that are crucial for tumor growth.
We examined whether susceptibility of mouse colon carcinoma (Colon 26) and rat gliosarcoma (9L) cells to 1-beta-D-arabiofuranosylcytonsine (AraC), a chemotherapeutic agent, can be increased after the tumor cells were transduced with the human dCK gene.
We demonstrate that gliosarcoma bears somatic alterations in gene coding for PI3K/Akt (<i>PTEN</i>, <i>PI3K</i>) and RAS/MAPK (<i>NF1</i>, <i>BRAF</i>) signaling pathways that are crucial for tumor growth.