Biopsy for diffuse intrinsic pontine glioma: a reappraisal

Kieran, Mark W.; Goumnerova, Liliana; Prados, Michael D.; Gupta, Nalin

doi:10.3171/2015.6.peds15374

Cited by 11 publications

(7 citation statements)

References 16 publications

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“…Given the high frequency and significant biological implications of histone H3 mutation in these tumors, “liquid biopsy” via CSF analysis may serve as an important approach for H3 mutation detection to impact patient treatment. Indeed, pre-clinical evaluation of agents aimed at the downstream effects of H3K27M in diffuse midline glioma demonstrate efficacy [11, 12, 27], and biopsy-based clinical trials for patient stratification to molecularly targeted treatments based on H3 mutation status are now underway [15, 17, 36]. However, while recent advances in neurosurgical and imaging techniques have made tumor biopsy for genetic analysis technically feasible, tissue acquisition from the brainstem or thalamus is not without risk, and brainstem glioma biopsy is not yet routinely performed.…”

Section: Discussionmentioning

confidence: 99%

Detection of Histone H3 mutations in cerebrospinal fluid-derived tumor DNA from children with diffuse midline glioma

Huang

Piunti

Lulla

et al. 2017

acta neuropathol commun

136

121

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Diffuse midline gliomas (including diffuse intrinsic pontine glioma, DIPG) are highly morbid glial neoplasms of the thalamus or brainstem that typically arise in young children and are not surgically resectable. These tumors are characterized by a high rate of histone H3 mutation, resulting in replacement of lysine 27 with methionine (K27M) in genes encoding H3 variants H3.3 (H3F3A) and H3.1 (HIST1H3B). Detection of these gain-of-function mutations has clinical utility, as they are associated with distinct tumor biology and clinical outcomes. Given the paucity of tumor tissue available for molecular analysis and relative morbidity of midline tumor biopsy, CSF-derived tumor DNA from patients with diffuse midline glioma may serve as a viable alternative for clinical detection of histone H3 mutation. We demonstrate the feasibility of two strategies to detect H3 mutations in CSF-derived tumor DNA from children with brain tumors (n = 11) via either targeted Sanger sequencing of H3F3A and HIST1H3B, or H3F3A c.83 A > T detection via nested PCR with mutation-specific primers. Of the six CSF specimens from children with diffuse midline glioma in our cohort, tumor DNA sufficient in quantity and quality for analysis was isolated from five (83%), with H3.3K27M detected in four (66.7%). In addition, H3.3G34V was identified in tumor DNA from a patient with supratentorial glioblastoma. Test sensitivity (87.5%) and specificity (100%) was validated via immunohistochemical staining and Sanger sequencing in available matched tumor tissue specimens (n = 8). Our results indicate that histone H3 gene mutation is detectable in CSF-derived tumor DNA from children with brain tumors, including diffuse midline glioma, and suggest the feasibility of "liquid biopsy" in lieu of, or to complement, tissue diagnosis, which may prove valuable for stratification to targeted therapies and monitoring treatment response.

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Section: Discussionmentioning

confidence: 99%

Detection of Histone H3 mutations in cerebrospinal fluid-derived tumor DNA from children with diffuse midline glioma

Huang

Piunti

Lulla

et al. 2017

acta neuropathol commun

136

121

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“…An example of research biopsies in other disease settings is diffuse intrinsic pontine glioma (DIPG), a devastating and rapidly fatal pediatric brain cancer that was once considered contraindicated for biopsy because of procedural risks, dismal prognosis, and the ability to make a clinical diagnosis non-invasively through MRI. 55–57 Now, in the context of clinical trials in which tissue will be used for research and to investigate biological markers for rational selection of treatment options, surgical biopsy for DIPG is ethically justifiable and included in randomized controlled trials (e.g., NCT01182350, NCT02233049). In nephrology, research biopsies in the absence of a clinical indication for CKD have been performed in diabetic nephropathy, 58,59 hypertensive kidney disease, 60 and Fabry disease.…”

Section: Research Biopsies In Other Contextsmentioning

confidence: 99%

Expanding the Role for Kidney Biopsies in Acute Kidney Injury

Waikar

McMahon

2018

Seminars in Nephrology

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Acute kidney injury (AKI) is a highly heterogeneous, common, and potentially devastating condition associated with markedly increased hospital length of stay, cost, mortality, and morbidity. Expanding the role for kidney biopsies in AKI may offer fresh insights into disease heterogeneity, molecular mechanisms, and therapeutic targets. A number of challenges face investigators and clinicians considering research biopsies in AKI: ensuring patient safety, ensuring the ethical conduct of research studies, and maximizing the scientific yield of the kidney tissue obtained. The societal benefits of research that lead to novel strategies for preventing and treating AKI would be enormous. Rethinking our current approach to the role of kidney biopsy for AKI diagnosis and research may be a major step toward the promise of personalized medicine in nephrology.

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“…However, stereotactic biopsy for pediatric brainstem tumors is associated with a low risk of complications and could be essential for individualizing treatment based on molecular profiling ( 4 ). The prognosis for these young patients is dire, with a median overall survival of only 12 months ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

DNX-2401, an Oncolytic Virus, for the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Gliomas: A Case Report

et al. 2018

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Diffuse intrinsic pontine gliomas (DIPGs) are aggressive glial brain tumors that primarily affect children, for which there is no curative treatment. Median overall survival is only one year. Currently, the scientific focus is on expanding the knowledge base of the molecular biology of DIPG, and identifying effective therapies. Oncolytic adenovirus DNX-2401 is a replication-competent, genetically modified virus capable of infecting and killing glioma cells, and stimulating an anti-tumor immune response. Clinical trials evaluating intratumoral DNX-2401 in adults with recurrent glioblastoma have demonstrated that the virus has a favorable safety profile and can prolong survival. Subsequently, these results have encouraged the transition of this biologically active therapy from adults into the pediatric population. To this aim, we have designed a clinical Phase I trial for newly diagnosed pediatric DIPG to investigate the feasibility, safety, and preliminary efficacy of delivering DNX-2401 into tumors within the pons following biopsy. This case report presents a pediatric patient enrolled in this ongoing Phase I trial for children and adolescents with newly diagnosed DIPG. The case involves an 8-year-old female patient with radiologically diagnosed DIPG who underwent stereotactic tumor biopsy immediately followed by intratumoral DNX-2401 in the same biopsy track. Because there were no safety concerns or new neurological deficits, the patient was discharged 3 days after the procedures. To our knowledge, this is the first report of intratumoral DNX-2401 for a patient with DIPG in a clinical trial. We plan to demonstrate that intratumoral delivery of an oncolytic virus following tumor biopsy for pediatric patients with DIPG is a novel and feasible approach and that DNX-2401 represents an innovative treatment for the disease.

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Biopsy for diffuse intrinsic pontine glioma: a reappraisal

Cited by 11 publications

References 16 publications

Detection of Histone H3 mutations in cerebrospinal fluid-derived tumor DNA from children with diffuse midline glioma

Detection of Histone H3 mutations in cerebrospinal fluid-derived tumor DNA from children with diffuse midline glioma

Expanding the Role for Kidney Biopsies in Acute Kidney Injury

DNX-2401, an Oncolytic Virus, for the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Gliomas: A Case Report

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