The prognostic significance of HIST1H3B/C and H3F3A K27M mutations in diffuse midline gliomas is influenced by patient age

Vuong, Huy Gia; Ngo, Tam N.M.; Le, Hieu Trong; Dunn, Ian F.

doi:10.1007/s11060-022-04027-2

Cited by 19 publications

(17 citation statements)

References 51 publications

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“…However, participants who underwent major debulking or total or near-total resection had longer overall survival (OS): 18.5 months vs. 11.4 months ( 14 ). Of note, since H3.1-mutant DMGs are primarily located in the pons and thalamus, the rate of tumor resection for these tumors is lower as compared to H3.3-mutated DMGs ( 46 ).…”

Section: A Complex Biological and Clinical Picture Behind A Unifying ...mentioning

confidence: 98%

“…in 2022 included 26 studies with 102 H3.1-mutant DMGs and H3.3-mutant DMGs. H3.1-K27M mutation confers a better prognosis than H3.3-K27M mutation in children, while in the adult population, H3.3-mutated tumors are associated with better survival ( 46 ).…”

Section: A Complex Biological and Clinical Picture Behind A Unifying ...mentioning

confidence: 99%

“…Similar results have been recorded by Vuong et al., who tried to stratify patients with H3K27 DMG among more than 800 patients (children and adults). They found that patients with thalamic and spinal cord tumors had significantly better survival than patients with brainstem tumors ( 46 ). Furthermore, unlike thalamic tumors, the presence of the H3K27M mutation in DIPG is a much weaker prognostic indicator: wild-type DIPG (approximately 15% of all biopsied cases) has the same unfavorable prognosis as H3K27M-mutant DIPG ( 63 ).…”

Section: A Complex Biological and Clinical Picture Behind A Unifying ...mentioning

confidence: 99%

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Pediatric diffuse midline glioma H3K27- altered: A complex clinical and biological landscape behind a neatly defined tumor type

Vallero

Bertero²,

Morana³

et al. 2023

Front. Oncol.

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The 2021 World Health Organization Classification of Tumors of the Central Nervous System, Fifth Edition (WHO-CNS5), has strengthened the concept of tumor grade as a combination of histologic features and molecular alterations. The WHO-CNS5 tumor type “Diffuse midline glioma, H3K27-altered,” classified within the family of “Pediatric-type diffuse high-grade gliomas,” incarnates an ideally perfect integrated diagnosis in which location, histology, and genetics clearly define a specific tumor entity. It tries to evenly characterize a group of neoplasms that occur primarily in children and midline structures and that have a dismal prognosis. Such a well-defined pathological categorization has strongly influenced the pediatric oncology community, leading to the uniform treatment of most cases of H3K27-altered diffuse midline gliomas (DMG), based on the simplification that the mutation overrides the histological, radiological, and clinical characteristics of such tumors. Indeed, multiple studies have described pediatric H3K27-altered DMG as incurable tumors. However, in biology and clinical practice, exceptions are frequent and complexity is the rule. First of all, H3K27 mutations have also been found in non-diffuse gliomas. On the other hand, a minority of DMGs are H3K27 wild-type but have a similarly poor prognosis. Furthermore, adult-type tumors may rarely occur in children, and differences in prognosis have emerged between adult and pediatric H3K27-altered DMGs. As well, tumor location can determine differences in the outcome: patients with thalamic and spinal DMG have significantly better survival. Finally, other concomitant molecular alterations in H3K27 gliomas have been shown to influence prognosis. So, when such additional mutations are found, which one should we focus on in order to make the correct clinical decision? Our review of the current literature on pediatric diffuse midline H3K27-altered DMG tries to address such questions. Indeed, H3K27 status has become a fundamental supplement to the histological grading of pediatric gliomas; however, it might not be sufficient alone to exhaustively define the complex biological behavior of DMG in children and might not represent an indication for a unique treatment strategy across all patients, irrespective of age, additional molecular alterations, and tumor location.

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Section: A Complex Biological and Clinical Picture Behind A Unifying ...mentioning

confidence: 98%

Section: A Complex Biological and Clinical Picture Behind A Unifying ...mentioning

confidence: 99%

Section: A Complex Biological and Clinical Picture Behind A Unifying ...mentioning

confidence: 99%

See 1 more Smart Citation

Pediatric diffuse midline glioma H3K27- altered: A complex clinical and biological landscape behind a neatly defined tumor type

Vallero

Bertero²,

Morana³

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

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“…High-grade glioma with the histone H3 mutation tends to occur in children but also in adolescents or young patients, most of whom are younger than 30 years. [12][13] The prognosis of H3F3A-mutant glioma has been reported with varying results in children and adults. [3][4][14][15][16] that the pediatric group has a favorable prognosis.…”

Section: Pathological Featuresmentioning

confidence: 99%

“…[3][4][14][15][16] that the pediatric group has a favorable prognosis. 12 Tumors with the H3 G34 mutation were consistently located within the cerebral hemisphere and frequently invaded the parietal and temporal lobes. 4 Interestingly, H3 K27 M-mutant diffuse midline gliomas in adults mainly involved the thalamus and spinal cord.…”

Section: Pathological Featuresmentioning

confidence: 99%

The clinicopathological features and prognosis of multifocal high-grade gliomas in adults withH3F3Amutation

Zhao

Chen

Wang

et al. 2023

NSJ

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The immune response behind peptide vaccination in diffuse midline glioma

Vincent,

Remeseiro

2024

Molecular Oncology

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A first‐in‐human trial demonstrated that a vaccine targeting the histone mutation H3K27M can induce an immune response, in a mutation‐specific manner, in patients with diffuse midline glioma. In a recent study by Boschert et al., the same group now dissects the functional immune response triggered after effective vaccination of one of the patients, who has been in remission for over 3 years. The H3K27M peptide vaccine, named H3‐vac, induces a CD4+ T‐cell‐specific immune response in this patient and expands the repertoire of polyclonal H3K27M‐specific T‐cell receptors. A clonal H3K27M‐reactive B‐cell population was also detected in the patient's cerebrospinal fluid. Importantly, the immune response is induced across various human leukocyte antigen alleleotypes, indicating the potential efficacy of the vaccine in diverse populations. By exploring in detail the immune response linked to this patient's long‐term survival, the authors prove peptide vaccinations as a viable therapeutic approach. This paves the way for personalised therapies harnessing immunogenic T‐ and B‐cell responses against different tumour types.

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The prognostic significance of HIST1H3B/C and H3F3A K27M mutations in diffuse midline gliomas is influenced by patient age

Cited by 19 publications

References 51 publications

Pediatric diffuse midline glioma H3K27- altered: A complex clinical and biological landscape behind a neatly defined tumor type

Pediatric diffuse midline glioma H3K27- altered: A complex clinical and biological landscape behind a neatly defined tumor type

The clinicopathological features and prognosis of multifocal high-grade gliomas in adults withH3F3Amutation

The immune response behind peptide vaccination in diffuse midline glioma

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