Diffuse Midline Gliomas With Histone H3 K27M Mutation in Adults and Children

Zheng, Linmao; Gong, Jianya; Yu, Tianping; Zou, Yutong; Zhang, Mengni; Nie, Ling; Chen, Xueqin; Ye, Qiang; Liu, Qing; Mao, Qing; Zhou, Qiao; Chen, Ni

doi:10.1097/pas.0000000000001897

Cited by 44 publications

(60 citation statements)

References 43 publications

(113 reference statements)

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“…Genetic tests concerning HIST1H3B/C were not included in this study. However, we believe that this had little effect on our result since H3K27me3, the trimethylated lysine 27 of histone could be downregulated by mutation of K27M in both H3.3 and H3.1 ( 9 ), were evaluated in all tumor samples and the rate of H3.1 K27M mutation in adult patients were lower than that of children ( 10 ).…”

Section: Discussionmentioning

confidence: 87%

H3K27M Mutation Doesn’t Mean Worse Prognosis in Old Patients

Nie

et al. 2022

Front. Oncol.

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ObjectiveDiffuse midline glioma (DMG), H3K27 altered is a new entity that has become widely recognized. However, studies concerning DMG in adult patients remain rare. We did a retrospective study covering the largest amount of patients to date to analyze the clinicopathological characteristics of diffuse glioma in midline structures of the adult.MethodsWe reviewed 108 cases of adult DMG, collected their clinical data, and pathological results including H3K27 mutation. Summarized their features and the connection with overall survival in different age groups.ResultsAmong 108 cases, 79 tumors were located at the thalamus. 38 patients had H3K27M mutation, whose average age was 35.7 years. The median overall survival of H3K27M-mutant gliomas and the 80 H3K27M wild-type gliomas were both 12 months. For young patients (age ≤ 35), The median survival time of the H3K27M-mutant was 18 months, while that of the H3K27M wild-type was 37 months. For older patients (age>35), the median survival time of the H3K27M-mutant was 16 months, while that of the H3K27M wild-type was 13 months. Other clinicopathological factors including sex, tumor location, the approach of surgery, histological grade, ATRX, and P53 were statistically irrelevant to prognosis.ConclusionThe DMG in adults mainly occurred in the thalamus. H3K27M mutations tend to happen more frequently in young adults, and this genetic alteration results in a worse outcome only in young patients (≤35). For old patients, age is the only independent prognostic factor. Patients who underwent different surgical operations including biopsy, subtotal resection, and total resection had similar prognoses.

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Section: Discussionmentioning

confidence: 87%

H3K27M Mutation Doesn’t Mean Worse Prognosis in Old Patients

Nie

et al. 2022

Front. Oncol.

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“…The enhancement patterns vary, but lesion enhancement is frequently not significant ( 9 - 11 ). The typical histology of DIPG is fibrous astrocytoma, in which cell anaplasia, increased mitotic activity, necrosis, and vascular proliferation are common ( 12 ). The imaging and histological features of this case were mostly consistent with the typical manifestations of DIPG.…”

Section: Discussionmentioning

confidence: 99%

“…The duration of clinical symptoms is similar between adults and children, but the long-term quality of life and survival time of adults is better than that of children ( 12 ). In addition, adult DMG commonly occurs in the thalamus, whereas pediatric DMG commonly occurs in the brainstem; the average tumor diameter is significantly larger in children than in adults ( 12 ). However, tumor enhancement, cystic changes, and cerebral edema were similar between adults and children ( 10 , 11 ).…”

Section: Discussionmentioning

confidence: 99%

A rare presentation of primary lateral ventricle H3 K27-altered diffuse midline glioma in a 14-year-old girl: a case description

Zhao¹,

Sun²,

Zhang³

et al. 2022

Quant Imaging Med Surg

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“…Rarer mutations have been reported in a minority of patients: PPM1D, PIK3CA, PIK3R1, PTEN, and ATRX ( 33 , 53 , 54 ). The prognostic meaning of all such additional molecular alterations in DMGs is still largely undefined, although some initial indications have emerged: in a retrospective study of 94 adults and 70 pediatric cases of diffuse midline glioma, age above 18 years (P=0.007), loss of ATRX expression (P=0.032), and Ki-67 index ≤5% (P=0.039) represented independent favorable prognosticators for longer survival across the entire cohort of H3K27M-mutant DMGs ( 55 ), while P53 overexpression has been identified as a negative prognostic factor for overall survival by multivariate analysis in another study ( 56 ).…”

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

confidence: 99%

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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Diffuse Midline Gliomas With Histone H3 K27M Mutation in Adults and Children

Cited by 44 publications

References 43 publications

H3K27M Mutation Doesn’t Mean Worse Prognosis in Old Patients

H3K27M Mutation Doesn’t Mean Worse Prognosis in Old Patients

A rare presentation of primary lateral ventricle H3 K27-altered diffuse midline glioma in a 14-year-old girl: a case description

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

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