Gliosarcomas lack BRAF^V600E mutation, but a subset exhibit β‐catenin nuclear localization

Abstract

Gliosarcoma (GS) is a rare subtype of glioblastoma (GBM) characterized by both glial and mesenchymal components. Unlike GBM, there are no specific prognostic markers, and optimized treatments for patients with GS do not exist. Recent reports describe BRAF mutation in malignant peripheral nerve sheath tumors, and aberrant Wnt signaling and CTNNB1 (β-catenin gene) mutations have been described in GBM. We sought to determine whether GS tumors harbor BRAF mutations or aberrant Wnt signaling, as indicated by nuclear localization of β-catenin, by immunohistochemical detection. Forty-eight (48) cases of primary and secondary adult GS (including recurrent ones) were evaluated by immunohistochemical techniques for the presence of nuclear β-catenin and the BRAF mutation. A small subset (6/46, 13%) showed nuclear localization of β-catenin. None of the cases harbored BRAF mutations (0/48). These results are the first to describe the presence of Wnt signaling pathway abnormalities, manifested by nuclear β-catenin, in a subset, as well as the lack of BRAF mutation in GS. We propose a potential role for Wnt pathway alterations in the pathogenesis of a subset of GS.

Gliosarcoma Is Driven by Alterations in PI3K/Akt, RAS/MAPK Pathways and Characterized by Collagen Gene Expression Signature

“…We also found the BRAFV600E mutation present in two patients (2/10, 20%), which is in contrast to the reported lack of BRAFV600E immunoreactivity in 48 gliosarcoma tumor sections [31], but in agreement with a recent finding [32]. Activating BRAF-V600E mutations are recurrently found in pediatric glial and glioneuronal brain tumors [12,33] and specific inhibitors are entering clinical trials.…”

A rare case of BRAF V600E‐mutated epithelioid glioblastoma with a sarcomatous component

“…Several brain tumors have been described to frequently harbor the BRAF V600E mutation, including pleomorphic xanthoastrocytoma (PXA) (60%), anaplastic PXA (60%), ganglioglioma (GG) (20–60%), extracerebellar pilocytic astrocytoma (20%), and E‐GBM (50%) . However, gliosarcoma with BRAF V600E is extremely rare (1%) . In our case, both the sarcomatous and epithelioid components harbored BRAF V600E, leading us to consider a diagnosis of E‐GBM with a sarcomatous component.…”

“…[5][6][7] However, gliosarcoma with BRAF V600E is extremely rare (1%). [7][8][9] In our case, both the sarcomatous and epithelioid components harbored BRAF V600E, leading us to consider a diagnosis of E-GBM with a sarcomatous component.…”

Oncogenic BRAF Alterations and Their Role in Brain Tumors

“…Initial studies suggested that BRAF mutations are absent in gliosarcomas. However, BRAF V600E mutations were first described in a few case reports [84,85] and later in a study applying next generation sequencing in 10 gliosarcomas, which revealed BRAF V600E mutations in 2 cases [86]. We recently analyzed a cohort of 75 gliosarcomas and only one case harbored a V600E mutation, making it comparably rare as in GBM [67].…”