Primary and secondary gliosarcomas: clinical, molecular and survival characteristics

Cachia, David; Kamiya-Matsuoka, Carlos; Mandel, Jacob; Olar, Adriana; Cykowski, Matthew D.; Armstrong, Terri S.; Fuller, Gregory N.; Gilbert, Mark R.; Groot, John F. de

doi:10.1007/s11060-015-1930-y

Cited by 62 publications

(72 citation statements)

References 44 publications

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“…Notwithstanding, limited but stepwise discoveries are optimizing treatment protocols, as in the specific example of GS frequently lacking the overexpression of epidermal growth factor receptor (EGFR) seen in IDH-wildtype GB, which challenges the utility of anti-EGFR modalities in GS treatment [19]. Still other studies of the molecular alterations in GS have found a high incidence of TP53 mutations, as well as rare EGFR and IDH mutations [20, 21]. Further study of the molecular mechanisms underlying GS development and spread is required to better understand the natural history and optimal treatment of these lethal tumors.…”

Section: Discussionmentioning

confidence: 99%

Gliosarcoma with Primary Skull Base Invasion

Nguyen

Perry

Graffeo

et al. 2016

Case Reports in Radiology

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Gliosarcoma is an uncommon variant of glioblastoma, which commonly demonstrates dural attachment. However, skull base invasion is rarely seen with this entity. Herein, we report a 44-year-old female patient diagnosed with primary intracranial gliosarcoma extensively invading the skull base and muscles of mastication. She presented to our institution with a three-month history of difficult right jaw opening and retro-orbital pressure and one week of severe right-sided postauricular headache. Head CT demonstrated a 6 cm mass with marked bony erosion. Brain MRI at a one-week interval more clearly characterized tumor extension through the right orbit and muscles of mastication, with overall growth to 7 cm and worsening midline shift. The patient underwent a right frontotemporal craniotomy for gross total resection. Pathology confirmed the diagnosis of gliosarcoma, IDH-wildtype (WHO grade IV). Her postoperative course was uneventful and she was discharged at preoperative neurologic baseline. To our knowledge, this is the third reported case of a primary intracranial gliosarcoma with direct invasion of skull base, brain parenchyma, and extracranial compartment. However, this is the first report case of primary GS invading the surrounding musculature and orbit. This case report highlights the rapid aggressiveness of gliosarcomas and further a prior undescribed radiographic and anatomic finding of skull base invasion with this entity.

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Section: Discussionmentioning

confidence: 99%

Gliosarcoma with Primary Skull Base Invasion

Nguyen

Perry

Graffeo

et al. 2016

Case Reports in Radiology

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“…PTEN mutations (15–45%), 4, 9, 10, 11 TP53 mutations (24–73%) 4, 9, 11 and TERT promoter mutations (83%) 10 were common, and IDH1 mutations were rare or absent (0–7%). 10, 11 At the chromosome level, the copy-number alterations (CNAs) that were commonly detected included amplifications of chromosome 7 (75%) and X (20%) as well as deletions of chromosome 10q (88%) and 9p (35%). 4, 10 Amplifications of EGFR and homozygous deletions of CDKN2A were reported in 0–8% 4, 9 and 37–60% 9, 10 of the GS cases, respectively.…”

Section: Introductionmentioning

confidence: 99%

High prevalence of TP53 mutations is associated with poor survival and an EMT signature in gliosarcoma patients

Cho

Park

et al. 2017

Exp Mol Med

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Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical genomic challenges because of its poor prognosis and limited genomic information. To gain a comprehensive view of the genomic alterations in GS and to understand the molecular etiology of GS, we applied whole-exome sequencing analyses for 28 GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin-fixed paraffin-embedded tissues for the validation set) and copy-number variation microarrays for 5 blood-matched fresh-frozen tissues. TP53 mutations were more prevalent in the GS cases (20/28, 70%) compared to the GBM cases (29/90, 32%), and the GS patients with TP53 mutations showed a significantly shorter survival (multivariate Cox analysis, hazard ratio=23.9, 95% confidence interval, 2.87–199.63, P=0.003). A pathway analysis showed recurrent alterations in MAPK signaling (EGFR, RASGRF2 and TP53), phosphatidylinositol/calcium signaling (CACNA1s, PLCs and ITPRs) and focal adhesion/tight junction (PTEN and PAK3) pathways. Genomic profiling of the matched recurrent GS cases detected the occurrence of TP53 mutations in two recurrent GS cases, which suggests that TP53 mutations play a role in treatment resistance. Functionally, we found that TP53 mutations are associated with the epithelial–mesenchymal transition (EMT) process of sarcomatous components of GS. 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.

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“…The molecular differences of primary IDH-wildtype and IDH-mutant (secondary) GBMs are well summarized in the paper by Cachia et al . [20]. The genetic abnormalities of the IDH-mutant GBMs are similar to grade II/III astrocytomas.…”

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confidence: 99%

Molecular Testing of Brain Tumor

Park

Won

Kim

et al. 2017

J Pathol Transl Med

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The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53, and ATRX, oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC, FUBP1, and the promoter region of telomerase reverse transcriptase (TERTp). IDH-wildtype (primary) glioblastomas typically lack mutations in IDH, but are characterized by copy number variations of EGFR, PTEN, CDKN2A/B, PDGFRA, and NF1 as well as mutations of TERTp. High-grade pediatric gliomas differ from those of adult gliomas, consisting of mutations in H3F3A, ATRX, and DAXX, but not in IDH genes. In contrast, well-circumscribed low-grade neuroepithelial tumors in children, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and ganglioglioma, often have mutations or activating rearrangements in the BRAF, FGFR1, and MYB genes. Other CNS tumors, such as ependymomas, neuronal and glioneuronal tumors, embryonal tumors, meningothelial, and other mesenchymal tumors have important genetic alterations, many of which are diagnostic, prognostic, and predictive markers and therapeutic targets. Therefore, the neuropathological evaluation of brain tumors is increasingly dependent on molecular genetic tests for proper classification, prediction of biological behavior and patient management. Identifying these gene abnormalities requires cost-effective and high-throughput testing, such as next-generation sequencing. Overall, this paper reviews the global guidelines and diagnostic algorithms for molecular genetic testing of brain tumors.

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Primary and secondary gliosarcomas: clinical, molecular and survival characteristics

Cited by 62 publications

References 44 publications

Gliosarcoma with Primary Skull Base Invasion

Gliosarcoma with Primary Skull Base Invasion

High prevalence of TP53 mutations is associated with poor survival and an EMT signature in gliosarcoma patients

Molecular Testing of Brain Tumor

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