K27M Mutation In Histone H3.3 Defines Clinically And Biologically ...

Trang chủ » H3.3 K27m » K27M Mutation In Histone H3.3 Defines Clinically And Biologically ...

Có thể bạn quan tâm

Clipboard, Search History, and several other advanced features are temporarily unavailable. Skip to main page content Dot gov

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation pubmed logo Search: Search Advanced Clipboard User Guide Save Email Send to
  • Clipboard
  • My Bibliography
  • Collections
  • Citation manager
Display options Display options Format Abstract PubMed PMID

Save citation to file

Format: Summary (text) PubMed PMID Abstract (text) CSV Create file Cancel

Email citation

Email address has not been verified. Go to My NCBI account settings to confirm your email and then refresh this page. To: Subject: Body: Format: Summary Summary (text) Abstract Abstract (text) MeSH and other data Send email Cancel

Add to Collections

  • Create a new collection
  • Add to an existing collection
Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an error Please try again Add Cancel

Add to My Bibliography

  • My Bibliography
Unable to load your delegates due to an error Please try again Add Cancel

Your saved search

Name of saved search: Search terms: Test search terms Would you like email updates of new search results? Saved Search Alert Radio Buttons
  • Yes
  • No
Email: (change) Frequency: Monthly Weekly Daily Which day? The first Sunday The first Monday The first Tuesday The first Wednesday The first Thursday The first Friday The first Saturday The first day The first weekday Which day? Sunday Monday Tuesday Wednesday Thursday Friday Saturday Report format: Summary Summary (text) Abstract Abstract (text) PubMed Send at most: 1 item 5 items 10 items 20 items 50 items 100 items 200 items Send even when there aren't any new results Optional text in email: Save Cancel

Create a file for external citation management software

Create file Cancel

Your RSS Feed

Name of RSS Feed: Number of items displayed: 5 10 15 20 50 100 Create RSS Cancel RSS Link Copy

Full text links

Springer full text link Springer Free PMC article Full text links

Actions

CiteCollectionsAdd to Collections
  • Create a new collection
  • Add to an existing collection
Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an errorPlease try again Add Cancel PermalinkPermalinkCopyDisplay options Display options Format AbstractPubMedPMID

Page navigation

  • Title & authors
  • Abstract
  • Figures
  • References
  • Publication types
  • MeSH terms
  • Substances
  • Grants and funding
  • LinkOut - more resources
Title & authors Abstract Figures References Publication types MeSH terms Substances Grants and funding LinkOut - more resources Full text links CiteDisplay options Display options Format AbstractPubMedPMID

Abstract

Pediatric glioblastomas (GBM) including diffuse intrinsic pontine gliomas (DIPG) are devastating brain tumors with no effective therapy. Here, we investigated clinical and biological impacts of histone H3.3 mutations. Forty-two DIPGs were tested for H3.3 mutations. Wild-type versus mutated (K27M-H3.3) subgroups were compared for HIST1H3B, IDH, ATRX and TP53 mutations, copy number alterations and clinical outcome. K27M-H3.3 occurred in 71 %, TP53 mutations in 77 % and ATRX mutations in 9 % of DIPGs. ATRX mutations were more frequent in older children (p < 0.0001). No G34V/R-H3.3, IDH1/2 or H3.1 mutations were identified. K27M-H3.3 DIPGs showed specific copy number changes, including all gains/amplifications of PDGFRA and MYC/PVT1 loci. Notably, all long-term survivors were H3.3 wild type and this group of patients had better overall survival. K27M-H3.3 mutation defines clinically and biologically distinct subgroups and is prevalent in DIPG, which will impact future therapeutic trial design. K27M- and G34V-H3.3 have location-based incidence (brainstem/cortex) and potentially play distinct roles in pediatric GBM pathogenesis. K27M-H3.3 is universally associated with short survival in DIPG, while patients wild-type for H3.3 show improved survival. Based on prognostic and therapeutic implications, our findings argue for H3.3-mutation testing at diagnosis, which should be rapidly integrated into the clinical decision-making algorithm, particularly in atypical DIPG.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1

K27M-H3.3 is associated with worse…

Fig. 1

K27M-H3.3 is associated with worse overall survival and higher age of diagnosis in…

Fig. 1 K27M-H3.3 is associated with worse overall survival and higher age of diagnosis in DIPG. a Kaplan–Meier curve of overall survival for all DIPG patients (n = 39). b DIPG patients carrying K27M-H3.3 mutation have worse overall survival compared to patients wild-type for this histone as determined by Kaplan–Meier analysis (Log-rank, p = 0.0027). Notably, all long term survivors were wild-type for H3F3A. c Age distribution of DIPG patients based on K27M-H3.3 mutational status. DIPG patients mutated for K27M-H3.3 have a higher age of diagnosis 8.13 years (±3.75) as compared to wild-type patients [4.57 years (±4.07), p = 0.010]
Fig. 2

Fig. 2

K27M-H3.3 is prevalent in DIPG…

Fig. 2

K27M-H3.3 is prevalent in DIPG and is associated with ATRX mutations mainly in…

Fig. 2 K27M-H3.3 is prevalent in DIPG and is associated with ATRX mutations mainly in older children. a Distribution of DIPG and supratentorial GBM based on H3.3 mutations suggests prevalence of K27M-H3.3 in DIPG. ATRX mutations in DIPG (b) and all location pediatric GBM (c) are significantly more prevalent in tumors from older children (mean ages 11.82 (±1.18) years and 16.91 ± 2.11, respectively) as compared to children with no ATRX mutation (mean ages of 5.20 (±0.81) years and 8.00 ± 0.69, respectively) (p = 0.02 and p < 0.0001, respectively)
Fig. 3

Fig. 3

Whole chromosome view of copy…

Fig. 3

Whole chromosome view of copy number alterations (CNA) in K27M-H3.3 mutants and wild-type…

Fig. 3 Whole chromosome view of copy number alterations (CNA) in K27M-H3.3 mutants and wild-type DIPG samples. a Similarities in CNA between both groups included loss of 10q, 11p, 13q and 14q as well as gains of 1q and 19q. However, major differences in copy number were identified with samples wild-type for K27M-H3.3 exhibiting gains of chromosome 2p and 7p as well as losses of chromosome 9p and 12q while samples mutants for K27M-H3.3 commonly exhibited loss of chromosome 5q, 6q, 17p and 21q. b Focal recurrent amplifications determined by GISTIC 2.0 analysis (q ≤ 0.05) show significant differences in focal gains between samples carrying K27M-H3.3 and samples wild type for H3.3. This included PDGFRA (4q12), MYV/PVT1 locus (8q24.21) gains and amplifications, which were exclusively identified in K27M-H3.3 mutants and ASAP2 (2p25.1) and MYCN (2p24.3) gains and amplifications which were exclusively identified in wild-type patients
See this image and copyright information in PMC

References

    1. Bartels U, Hawkins C, Vezina G, Kun L, Souweidane M, Bouffet E. Proceedings of the diffuse intrinsic pontine glioma (DIPG) Toronto Think Tank: advancing basic and translational research and cooperation in DIPG. J Neurooncol. 2011;105:119–125. doi: 10.1007/s11060-011-0704-4. - DOI - PubMed
    1. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006;125:315–326. doi: 10.1016/j.cell.2006.02.041. - DOI - PubMed
    1. Bouffet E, Tabori U, Huang A, Bartels U. Possibilities of new therapeutic strategies in brain tumors. Cancer Treat Rev. 2010;36:335–341. doi: 10.1016/j.ctrv.2010.02.009. - DOI - PubMed
    1. Broniscer A, Baker SJ, West AN, Fraser MM, Proko E, Kocak M, Dalton J, Zambetti GP, Ellison DW, Kun LE, Gajjar A, Gilbertson RJ, Fuller CE. Clinical and molecular characteristics of malignant transformation of low-grade glioma in children. J Clin Oncol. 2007;25:682–689. doi: 10.1200/JCO.2006.06.8213. - DOI - PubMed
    1. Bueno C, Montes R, Catalina P, Rodriguez R, Menendez P. Insights into the cellular origin and etiology of the infant pro-B acute lymphoblastic leukemia with MLL-AF4 rearrangement. Leukemia. 2011;25:400–410. doi: 10.1038/leu.2010.284. - DOI - PubMed
Show all 26 references

Publication types

  • Research Support, Non-U.S. Gov't Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search

MeSH terms

  • Adolescent Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Brain Stem Neoplasms / genetics* Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Brain Stem Neoplasms / mortality Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Brain Stem Neoplasms / pathology Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Child Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Child, Preschool Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Female Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Gene Expression Profiling Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Glioma / genetics* Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Glioma / mortality Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Glioma / pathology Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Histones / genetics* Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Humans Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Infant Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Male Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Mutation Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Pons / pathology* Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Prognosis Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Survival Rate Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search

Substances

  • Histones Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search

Grants and funding

  • MOP 115004/Canadian Institutes of Health Research/Canada

LinkOut - more resources

  • Full Text Sources

    • Europe PubMed Central
    • PubMed Central
    • Springer

  • Other Literature Sources

    • The Lens - Patent Citations Database

  • Research Materials

    • NCI CPTC Antibody Characterization Program

  • Miscellaneous

    • NCI CPTAC Assay Portal
Full text links [x] Springer full text link Springer Free PMC article [x] Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM Send To
  • Clipboard
  • Email
  • Save
  • My Bibliography
  • Collections
  • Citation Manager
[x]

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

Từ khóa » H3.3 K27m