Pilocytic astrocytoma and glioneuronal tumor with histone H3 K27M mutation

Orillac, Cordelia; Thomas, Cheddhi; Dastagirzada, Yosef; Hidalgo, Eveline Teresa; Golfinos, John G.; Zagzag, David; Wisoff, Jeffrey H.; Karajannis, Matthias A.; Snuderl, Matija

doi:10.1186/s40478-016-0361-0

Cited by 84 publications

(43 citation statements)

References 6 publications

(6 reference statements)

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“…The second case was a 10‐year‐old girl with glioneuronal tumor harboring a K27M mutation in the midbrain. Histological evaluation showed small round cells exhibiting neuropil‐like islands and rosettes . In a retrospective study, Solomon et al found a diffuse midline glioma arising in the thalamus of a 27‐year‐old woman which contained PNET‐like appearance .…”

Section: Discussionmentioning

confidence: 50%

Diffuse midline gliomas with histone H3‐K27M mutation: A rare case with PNET‐like appearance and neuropil‐like islands

Gao

Feng

et al. 2017

Neuropathology

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Diffuse midline glioma with histone H3-K27M mutation is a new tumor entity defined by the 2016 WHO Classification of Tumors of the Central Nervous System. A 51-year-old Chinese woman presented with neck pain for a month. Subsequent MRI revealed an intramedullary neoplasm extending from C5 to C7. Histologically, the cellular area of the tumor was composed of primitive, poorly differentiated, small cells with scant cytoplasm, nuclear molding, and brisk mitotic activity, exhibiting PNET-like appearance, while in the hypocellular area, oligodendroglioma-like cells were observed. More importantly, neuropil-like islands were observed in the cellular area. Microvascular proliferation was noted, with no necrosis. Besides histone H3K27M mutation, immunohistochemical staining also showed that the tumor cells were positive for oligodendrocyte lineage transcription factor 2 and ATRX. The neuropil-like areas were positive for synaptophysin, intermingled with scattered neuronal nuclear antigen positive cells. The Ki-67 proliferation index was about 30%, and tumor cells were highly immunopositive for p53. Sequencing for IDH1 codon 132 and IDH2 codon 172 gene mutations showed negative results. Furthermore, fluorescent analysis revealed 1p deletion in the lesion but no 19q deletion. Based on these findings, the tumor was diagnosed as diffuse midline gliomas with histone H3-K27M mutation in the spinal cord, corresponding to WHO grade IV. After 4 months of remission, the tumor recurred; 2 months later, the patient died. Herein, we report an extremely rare case of diffuse midline glioma with histone H3K27M mutation, which was morphologically characterized simultaneously by primitive neuroectodermal tumor-like appearance and neuropil-like islands.

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Section: Discussionmentioning

confidence: 50%

Diffuse midline gliomas with histone H3‐K27M mutation: A rare case with PNET‐like appearance and neuropil‐like islands

Gao

Feng

et al. 2017

Neuropathology

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“…Methylation profiles were compared to a reference cohort of 2150 cases from 77 tumor entities previously profiled and analyzed at German Cancer Research Center using a random forest algorithm and customized bioinformatics packages. In addition, the array data was used to calculate a low-resolution copy number profile (CNP) as previously described by others [7,8] and us [9,10]. Analysis was performed on specimens at the time of initial diagnosis.…”

Section: Genome-wide Methylation Profilingmentioning

confidence: 99%

Rapid progression to glioblastoma in a subset of IDH-mutated astrocytomas: a genome-wide analysis

et al. 2017

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According to the recently updated World Health Organization (WHO) classification (2016), grade II-III astrocytomas are divided into IDH-wildtype and IDH-mutant groups, the latter being significantly less aggressive in terms of both progression-free and total survival. We identified a small cohort of WHO grade II-III astrocytomas that harbored the IDH1 R132H mutation, as confirmed by both immunohistochemistry and molecular sequence analysis, which nonetheless had unexpectedly rapid recurrence and subsequent progression to glioblastoma. Among these four cases, the mean time to recurrence as glioblastoma was only 16 months and the mean total survival among the three patients who have died during the follow-up was only 31 months. We hypothesized that these tumors had other, unfavorable genetic or epigenetic alterations that negated the favorable effect of the IDH mutation. We applied genome-wide profiling with a methylation array (Illumina Infinium Human Methylation 450k) to screen for genetic and epigenetic alterations in these tumors. As expected, the methylation profiles of all four tumors were found to match most closely with IDH-mutant astrocytomas. Compared with a control group of four indolent, age-similar WHO grade II-III astrocytomas, the tumors showed markedly increased levels of overall copy number changes, but no consistent specific genetic alterations were seen across all of the tumors. While most IDH-mutant WHO grade II-III astrocytomas are relatively indolent, a subset may rapidly recur and progress to glioblastoma. The precise underlying cause of the increased aggressiveness in these gliomas remains unknown, although it may be associated with increased genomic instability.

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“…However, rare cases of H3 K27M mutant grade I GG and pilocytic astrocytomas were recently described, suggesting that H3 K27M mutations may be present in a spectrum of glial tumors. H3 K27M mutations should not be used as the sole criterion for the diagnosis of WHO Grade IV midline gliomas (19,29). In one of these cases, the H3 K27M mutation was associated with a BRAF V600E mutation.…”

Section: Introductionmentioning

confidence: 99%

Co‐occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma

Pagès

Beccaria²,

Boddaert³

et al. 2017

Brain Pathology

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Ganglioglioma (GG) is a grade I tumor characterized by alterations in the MAPK pathway, including BRAF V600E mutation. Recently, diffuse midline glioma with an H3 K27M mutation was added to the WHO 2016 classification as a new grade IV entity. As cooccurrence of H3 K27M and BRAF V600E mutations has been reported in midline tumors and anaplastic GG, we searched for BRAF V600E and H3 K27M mutations in a series of 54 paediatric midline grade I GG (midline GG) to determine the frequency of double mutations and its relevance for prognosis. Twenty-seven patients (50%) possessed the BRAF V600E mutation. The frequency of the co-occurrence of H3F3A/BRAF mutations at diagnosis was 9.3%. No H3 K27M mutation was detected in the absence of the BRAF V600E mutation. Double-immunostaining revealed that BRAF V600E and H3 K27M mutant proteins were present in both the glial and neuronal components. Immunopositivity for the BRAF V600E mutant protein correlated with BRAF mutation status as detected by massARRAY or digital droplet PCR. The median follow-up of patients with double mutation was 4 years. One patient died of progressive disease 8 years after diagnosis, whereas the four other patients were all alive with stable disease at the last clinical follow-up (at 9 months, 1 year and 7 years) without adjuvant therapy. We demonstrate in this first series of midline GGs that the H3 K27M mutation can occur in association with the BRAF V600E mutation in grade I glioneuronal tumors. Despite the presence of H3 K27M mutations, these cases should not be graded and treated as grade IV tumors because they have a better spontaneous outcome than classic diffuse midline H3 K27M-mutant glioma. These data suggest that H3 K27M cannot be considered a specific hallmark of grade IV diffuse gliomas and highlight the importance of integrated histomolecular diagnosis in paediatric brain tumors.

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Pilocytic astrocytoma and glioneuronal tumor with histone H3 K27M mutation

Cited by 84 publications

References 6 publications

Diffuse midline gliomas with histone H3‐K27M mutation: A rare case with PNET‐like appearance and neuropil‐like islands

Diffuse midline gliomas with histone H3‐K27M mutation: A rare case with PNET‐like appearance and neuropil‐like islands

Rapid progression to glioblastoma in a subset of IDH-mutated astrocytomas: a genome-wide analysis

Co‐occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma

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