Spatial genomic heterogeneity in diffuse intrinsic pontine and midline high-grade glioma: implications for diagnostic biopsy and targeted therapeutics View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-01-04

AUTHORS

Lindsey M. Hoffman, Mariko DeWire, Scott Ryall, Pawel Buczkowicz, James Leach, Lili Miles, Arun Ramani, Michael Brudno, Shiva Senthil Kumar, Rachid Drissi, Phillip Dexheimer, Ralph Salloum, Lionel Chow, Trent Hummel, Charles Stevenson, Q. Richard Lu, Blaise Jones, David Witte, Bruce Aronow, Cynthia E. Hawkins, Maryam Fouladi

ABSTRACT

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) and midline high-grade glioma (mHGG) are lethal childhood brain tumors. Spatial genomic heterogeneity has been well-described in adult HGG but has not been comprehensively characterized in pediatric HGG. We performed whole exome sequencing on 38-matched primary, contiguous, and metastatic tumor sites from eight children with DIPG (n = 7) or mHGG (n = 1) collected using a unique MRI-guided autopsy protocol. Validation was performed using Sanger sequencing, Droplet Digital polymerase-chain reaction, immunohistochemistry, and fluorescent in-situ hybridization. RESULTS: Median age at diagnosis was 6.1 years (range: 2.9-23.3 years). Median overall survival was 13.2 months (range: 11.2-32.2 months). Contiguous tumor infiltration and distant metastases were observed in seven and six patients, respectively, including leptomeningeal dissemination in three DIPGs. Histopathological heterogeneity was evident in seven patients, including intra-pontine heterogeneity in two DIPGs, ranging from World Health Organization grade II to IV astrocytoma. We found conservation of heterozygous K27M mutations in H3F3A (n = 4) or HIST1H3B (n = 3) across all primary, contiguous, and metastatic tumor sites in all DIPGs. ACVR1 (n = 2), PIK3CA (n = 2), FGFR1 (n = 2), and MET (n = 1) were also intra-tumorally conserved. ACVR1 was co-mutated with HIST1H3B (n = 2). In contrast, PDGFRA amplification and mutation were spatially heterogeneous, as were mutations in BCOR (n = 1), ATRX (n = 2), and MYC (n = 1). TP53 aberrations (n = 3 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved. CONCLUSION: Spatial conservation of prognostically-relevant and therapeutically-targetable somatic mutations in DIPG and mHGG contrasts the significant heterogeneity of driver mutations seen in adult HGG and supports uniform implementation of diagnostic biopsy in DIPG and mHGG to classify molecular risk groups and guide therapeutic strategy. More... »

PAGES

1

References to SciGraph publications

  • 2015-09-23. Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes in ACTA NEUROPATHOLOGICA
  • 2015-04-13. Mutational landscape and clonal architecture in grade II and III gliomas in NATURE GENETICS
  • 2014-04-06. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations in NATURE GENETICS
  • 2014-01-30. Prognostic significance of telomere maintenance mechanisms in pediatric high-grade gliomas in JOURNAL OF NEURO-ONCOLOGY
  • 2007-11-15. Variation of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in serial samples in glioblastoma in JOURNAL OF NEURO-ONCOLOGY
  • 2014-07-22. Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications in ACTA NEUROPATHOLOGICA
  • 2006-03-28. Incidence and patterns of neuraxis metastases in children with diffuse pontine glioma★ in JOURNAL OF NEURO-ONCOLOGY
  • 2012-01-29. Somatic Histone H3 Alterations in Paediatric Diffuse Intrinsic Pontine Gliomas and Non-Brainstem Glioblastomas in NATURE GENETICS
  • 2010-07-10. Prospective neuraxis MRI surveillance reveals a high risk of leptomeningeal dissemination in diffuse intrinsic pontine glioma in JOURNAL OF NEURO-ONCOLOGY
  • 2014-05-03. Diffuse intrinsic pontine glioma: a reassessment in JOURNAL OF NEURO-ONCOLOGY
  • 2014-11-17. Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma in NATURE MEDICINE
  • 2012-06-03. K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas in ACTA NEUROPATHOLOGICA
  • 2014-06-15. Subventricular spread of diffuse intrinsic pontine glioma in ACTA NEUROPATHOLOGICA
  • 2015-09-09. Biopsy in a series of 130 pediatric diffuse intrinsic Pontine gliomas in CHILD'S NERVOUS SYSTEM
  • 2014-04-06. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma in NATURE GENETICS
  • 2014-04-06. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma in NATURE GENETICS
  • 2015-05-04. Functionally-defined Therapeutic Targets in Diffuse Intrinsic Pontine Glioma in NATURE MEDICINE
  • 2014-04-06. Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma in NATURE GENETICS
  • 2012-01-29. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s40478-015-0269-0

    DOI

    http://dx.doi.org/10.1186/s40478-015-0269-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1033490454

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26727948


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