H3F3A K27M mutations in thalamic gliomas from young adult patients

Aihara, Koki; Mukasa, Akitake; Gotoh, Kengo; Saito, Kuniaki; Nagae, Genta; Tsuji, Shingo; Tatsuno, Kenji; Yamamoto, Shozo; Takayanagi, Shunsaku; Narita, Yoshitaka; Shibui, Soichiro; Aburatani, Hiroyuki; Saito, Nobuhito

doi:10.1093/neuonc/not144

Cited by 155 publications

(158 citation statements)

References 24 publications

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“…Highly recurrent mutations in genes that encode H3 histone proteins, which are involved in chromatin function and gene expression regulation, occur in about 38% of childhood and young adult (age ≤ 30 years) HGGs but are not seen in HGGs of older patients [4,10] . Conversely, IDH mutations, which are commonly found in adult gliomas, are extremely rare in children and essentially mutually exclusive with H3 histone mutations [8,9] .…”

Section: Discussionmentioning

confidence: 99%

“…In addition to producing a mutant K27M form of histone H3 that can be detected by immunohistochemistry [12] , the alteration stimulates tumorigenesis via a multitude of changes that impact DNA transcription, replication, and repair [9,11] . HGGs with histone-encoding genes that harbor K27M mutations commonly arise in midline CNS structures and have been found in over 70% of diffuse gliomas originating from the brain stem, especially the pons, as well as in about half of gliomas arising in the spinal cord and thalamus [3][4][5][6] . A study by Solomon et al [1] that sought to characterize the anatomic locations and age range of DMG-K27Ms found that histone H3-K27M mutations were present in 64% of pediatric and adult diffuse gliomas involving midline structures, predominantly the brainstem, thalamus, and spinal cord, with few examples arising in the cerebellum, third ventricle, and hypothalamus.…”

Section: Color Version Available Onlinementioning

confidence: 99%

“…This devastating neoplasm arises in midline structures of the central nervous system (CNS) and commonly involves the brain stem (e.g. brain stem gliomas), including the majority of diffuse intrinsic pontine gliomas (DIPGs) [1,3] , as well as the thalamus [1,4] and spinal cord [1,5,6] .…”

Section: Introductionmentioning

confidence: 99%

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Extending the Neuroanatomic Territory of Diffuse Midline Glioma, K27M Mutant: Pineal Region Origin

et al. 2017

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Diffuse midline glioma, H3-K27M mutant (DMG-K27M) is a newly described, molecularly distinct infiltrative glioma that almost exclusively arises in midline CNS structures, including the brain stem, especially the pons, as well as the thalamus and spinal cord with rare examples seen in the cerebellum, third ventricle, and hypothalamus. To our knowledge, only 1 case of a molecularly confirmed DMG-K27M arising in the pineal region has been previously reported. We present the second occurrence of a tissue-confirmed DMG-K27M of the pineal region, which, to our knowledge, is the first case reported in a child and the first case with documented preoperative MRI. This case, in addition to a prior report described in an adult, defines the lower end of a broad age range of DMG-K27M onset (12-65 years) and establishes the pineal gland as a bona fide site of origin for this newly codified midline glioma.

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Section: Discussionmentioning

confidence: 99%

Section: Color Version Available Onlinementioning

confidence: 99%

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Extending the Neuroanatomic Territory of Diffuse Midline Glioma, K27M Mutant: Pineal Region Origin

et al. 2017

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“…34 Methylation of the methylguanine methyltransferase gene (MGMT) and p53 overexpression have been identified in a subset of high-grade infiltrating thalamic gliomas that, along with elevated proliferation, appear to correlate with particularly poor outcome. 33 Recently, H3K27M mutations have been detected in a significant subset (65%-90%) of high-grade pediatric and young adult thalamic DAs, 35,36 placing them firmly in the genetically defined category of diffuse midline glioma. These tumors are defined by the 1, 4, 6-9, 12, 13, 15, 18, 19, 31, 32.…”

Section: Diffuse Astrocytomamentioning

confidence: 99%

Pediatric Thalamic Gliomas: An Updated Review

Gupta¹,

Shaller

McFadden³

2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Neoplasms originating in the thalamus are rare overall (1% of all brain tumors); however, they comprise approximately 5% of pediatric intracranial tumors and approach 15% of all malignant pediatric intracranial tumors in some series.Objective.-To update readers about the current understanding of the diverse histology, biology, and behavior of pediatric thalamic tumors. Histologic verification is now thought to be critical for planning treatment, and, as a result, biopsy and total/subtotal resections are much more common today than in the past.Data Sources.-A PubMed search using the keywords ''pediatric þ thalamic þ glioma'' yielded 45 publications with a total of 445 cases of thalamic gliomas in patients less than 18 years of age. We found only 9 substantial institutional series tabulating all encountered thalamic histologic types in children. This survey confirmed a high proportion of astrocytomas, 81% (214 of 265), of which approximately two-thirds were diffuse astrocytomas (146 of 214) and one-third were pilocytic astrocytomas (68 of 214). Of the diffuse astrocytomas, 34% (49 of 146) were low grade (World Health Organization grade II) and 55% (81 of 146) were high grade (World Health Organization grade III or IV), making the latter subgroup the largest single category of all pediatric thalamic tumors. Oligodendrogliomas and ependymomas (mostly anaplastic in both cases) comprised 10% and 3% of all pediatric thalamic tumors, respectively.Conclusions.-Tissue diagnosis is now thought crucial for prognostication and treatment, particularly as more potentially therapeutic molecular targets are discovered. Secure diagnosis allows identification of tumors for which resection is more feasible and beneficial.

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“…Furthermore, these different mutations also appear to segregate with distinct types of tumors. For instance, the K27M mutation has been found only in pediatric diffuse intrinsic pontine glioma (DIPG) and highgrade astrocytomas primarily restricted to midline locations (spinal cord, thalamus, pons, brainstem) in children and younger adults (11)(12)(13)(14)(15)(16)(17). The majority of K36M mutation has been found in chondroblastoma, and to a lesser extent, in clear-cell chondrosarcoma (9).…”

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confidence: 99%

Histone H3.3 and cancer: A potential reader connection

Lan

Shi

2014

Proc. Natl. Acad. Sci. U.S.A.

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The building block of chromatin is nucleosome, which consists of 146 base pairs of DNA wrapped around a histone octamer composed of two copies of histone H2A, H2B, H3, and H4. Significantly, the somatic missense mutations of the histone H3 variant, H3.3, are associated with childhood and young-adult tumors, such as pediatric high-grade astrocytomas, as well as chondroblastoma and giantcell tumors of the bone. The mechanisms by which these histone mutations cause cancer are by and large unclear. Interestingly, two recent studies identified BS69/ZMYND11, which was proposed to be a candidate tumor suppressor, as a specific reader for a modified form of H3.3 (H3.3K36me3). Importantly, some H3.3 cancer mutations are predicted to abrogate the H3.3K36me3/BS69 interaction, suggesting that this interaction may play an important role in tumor suppression. These new findings also raise the question of whether H3.3 cancer mutations may lead to the disruption and/or gain of interactions of additional cellular factors that contribute to tumorigenesis.histone | H3.3 | H3.3K36me3 | cancer | BS69

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H3F3A K27M mutations in thalamic gliomas from young adult patients

Abstract: We found that high-grade thalamic gliomas from young adults, like those from children and adolescents, frequently had H3F3A K27M.

Cited by 155 publications

References 24 publications

Extending the Neuroanatomic Territory of Diffuse Midline Glioma, K27M Mutant: Pineal Region Origin

Extending the Neuroanatomic Territory of Diffuse Midline Glioma, K27M Mutant: Pineal Region Origin

Pediatric Thalamic Gliomas: An Updated Review

Histone H3.3 and cancer: A potential reader connection

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