Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma

NCT01106794 | Recruiting

• 1 other identifier: DIPG-1
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to prospectively collect specimens from pediatric patients with diffuse intrinsic pontine glioma or brainstem glioma, either during therapy or at autopsy, in order to characterize the molecular abnormalities of this tumor.

Conditions

Diffuse Intrinsic Pontine Glioma; Brainstem Glioma

Keywords

diffuse intrinsic pontine glioma; DIPG; childhood brainstem glioma; pediatric brainstem glioma; brainstem glioma; BSG

Outcome Measures

Primary Outcomes (6)

• Genome-wide expression patterns of RNA in tumor samples, normal brainstem tissue and cerebrospinal fluid using Affymetrix gene expression profiling

  Collected tumor and normal samples will potentially be used for RNA genome-wide expression pattern profiling.

  5 years

• Validation of results of the genome-wide analysis

  The molecular analysis done on collected samples will be validated through whole genome sequencing.

  5 years

• Proteomic profiling of tumor, normal brainstem tissue and cerebrospinal fluid

  To obtain full characterization of collected samples, proteomic profiling will be done on tumor and normal samples collected.

  5 years

• Protein expression patterns as assessed by immunohistochemistry and western blot compared to normal brainstem tissue

  Collected tumor and normal samples will have the immunochemistry and western blot compared to assess protein expression variation.

  5 years

• Genome-wide analysis of tumor samples and normal brainstem tissue

  To obtain full characterization of collected samples, whole genome sequencing will be done on tumor and normal samples collected.

  5 years

• In vitro and in vivo molecular analysis of collected samples

  Collected samples will potentially be used for in vitro analysis and generation of animal models of this tumor.

  5 years

Secondary Outcomes (1)

• Assess aspects associated with specimen acquisition, including potential benefits and drawbacks

  5 years

Study Arms (1)

Patient samples

Fresh-frozen and fixed tumor samples, correspondent normal brain tissue samples, cerebrospinal fluid, urine, and serum samples from patients affected with diffuse intrinsic pontine glioma or brainstem glioma

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Community sample

You may qualify if:

• Patients of any age with clinical and radiologic diagnosis of diffuse intrinsic pontine glioma
• Patients with other high-grade gliomas originating in the brainstem
• Patients with focal gliomas (WHO grade I/II) of the brainstem

You may not qualify if:

• Patients with any type of infiltrative low grade (WHO grade I and II) or high grade glioma (WHO grade III and IV) originating outside the brainstem
• Patients harboring primary brainstem tumors with other histologic diagnoses (e.g., PNET)

Sponsors & Collaborators

• Children's National Research Institute: lead

Study Sites (1)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Related Publications (11)

• Becher OJ, Hambardzumyan D, Walker TR, Helmy K, Nazarian J, Albrecht S, Hiner RL, Gall S, Huse JT, Jabado N, MacDonald TJ, Holland EC. Preclinical evaluation of radiation and perifosine in a genetically and histologically accurate model of brainstem glioma. Cancer Res. 2010 Mar 15;70(6):2548-57. doi: 10.1158/0008-5472.CAN-09-2503. Epub 2010 Mar 2.

  PMID: 20197468 BACKGROUND

• Panditharatna E, Yaeger K, Kilburn LB, Packer RJ, Nazarian J. Clinicopathology of diffuse intrinsic pontine glioma and its redefined genomic and epigenomic landscape. Cancer Genet. 2015 Jul-Aug;208(7-8):367-73. doi: 10.1016/j.cancergen.2015.04.008. Epub 2015 May 1.

  PMID: 26206682 BACKGROUND

• Yadavilli S, Scafidi J, Becher OJ, Saratsis AM, Hiner RL, Kambhampati M, Mariarita S, MacDonald TJ, Codispoti KE, Magge SN, Jaiswal JK, Packer RJ, Nazarian J. The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma. Oncotarget. 2015 May 20;6(14):12141-55. doi: 10.18632/oncotarget.3716.

  PMID: 25987129 BACKGROUND

• Kambhampati M, Perez JP, Yadavilli S, Saratsis AM, Hill AD, Ho CY, Panditharatna E, Markel M, Packer RJ, Nazarian J. A standardized autopsy procurement allows for the comprehensive study of DIPG biology. Oncotarget. 2015 May 20;6(14):12740-7. doi: 10.18632/oncotarget.3374.

  PMID: 25749048 BACKGROUND

• Kambhampati M, Panditharatna E, Yadavilli S, Saoud K, Lee S, Eze A, Almira-Suarez MI, Hancock L, Bonner ER, Gittens J, Stampar M, Gaonkar K, Resnick AC, Kline C, Ho CY, Waanders AJ, Georgescu MM, Rance NE, Kim Y, Johnson C, Rood BR, Kilburn LB, Hwang EI, Mueller S, Packer RJ, Bornhorst M, Nazarian J. Harmonization of postmortem donations for pediatric brain tumors and molecular characterization of diffuse midline gliomas. Sci Rep. 2020 Jul 2;10(1):10954. doi: 10.1038/s41598-020-67764-2.

  PMID: 32616776 BACKGROUND

• Ballester LY, Wang Z, Shandilya S, Miettinen M, Burger PC, Eberhart CG, Rodriguez FJ, Raabe E, Nazarian J, Warren K, Quezado MM. Morphologic characteristics and immunohistochemical profile of diffuse intrinsic pontine gliomas. Am J Surg Pathol. 2013 Sep;37(9):1357-64. doi: 10.1097/PAS.0b013e318294e817.

  PMID: 24076776 RESULT

• Saratsis AM, Yadavilli S, Magge S, Rood BR, Perez J, Hill DA, Hwang E, Kilburn L, Packer RJ, Nazarian J. Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of cerebrospinal fluid. Neuro Oncol. 2012 May;14(5):547-60. doi: 10.1093/neuonc/nos067. Epub 2012 Apr 5.

  PMID: 22492959 RESULT

• Ahsan S, Raabe EH, Haffner MC, Vaghasia A, Warren KE, Quezado M, Ballester LY, Nazarian J, Eberhart CG, Rodriguez FJ. Increased 5-hydroxymethylcytosine and decreased 5-methylcytosine are indicators of global epigenetic dysregulation in diffuse intrinsic pontine glioma. Acta Neuropathol Commun. 2014 Jun 3;2:59. doi: 10.1186/2051-5960-2-59.

  PMID: 24894482 RESULT

• Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M, Morrison A, Lewis P, Bouffet E, Bartels U, Zuccaro J, Agnihotri S, Ryall S, Barszczyk M, Chornenkyy Y, Bourgey M, Bourque G, Montpetit A, Cordero F, Castelo-Branco P, Mangerel J, Tabori U, Ho KC, Huang A, Taylor KR, Mackay A, Bendel AE, Nazarian J, Fangusaro JR, Karajannis MA, Zagzag D, Foreman NK, Donson A, Hegert JV, Smith A, Chan J, Lafay-Cousin L, Dunn S, Hukin J, Dunham C, Scheinemann K, Michaud J, Zelcer S, Ramsay D, Cain J, Brennan C, Souweidane MM, Jones C, Allis CD, Brudno M, Becher O, Hawkins C. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet. 2014 May;46(5):451-6. doi: 10.1038/ng.2936. Epub 2014 Apr 6.

  PMID: 24705254 RESULT

• Saratsis AM, Kambhampati M, Snyder K, Yadavilli S, Devaney JM, Harmon B, Hall J, Raabe EH, An P, Weingart M, Rood BR, Magge SN, MacDonald TJ, Packer RJ, Nazarian J. Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine glioma reveals distinct molecular subtypes. Acta Neuropathol. 2014;127(6):881-95. doi: 10.1007/s00401-013-1218-2. Epub 2013 Dec 3.

  PMID: 24297113 RESULT

• Nikbakht H, Panditharatna E, Mikael LG, Li R, Gayden T, Osmond M, Ho CY, Kambhampati M, Hwang EI, Faury D, Siu A, Papillon-Cavanagh S, Bechet D, Ligon KL, Ellezam B, Ingram WJ, Stinson C, Moore AS, Warren KE, Karamchandani J, Packer RJ, Jabado N, Majewski J, Nazarian J. Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma. Nat Commun. 2016 Apr 6;7:11185. doi: 10.1038/ncomms11185.

  PMID: 27048880 RESULT

Related Links

• Children's National Medical Center

Biospecimen

Retention: SAMPLES WITH DNA

Cerebrospinal fluid, serum, urine, brainstem tumor and constitutional tissue from patients with diffuse intrinsic pontine glioma or brainstem glioma will be collected.

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Javad Nazarian, PhD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Javad Nazarian, PhD

CONTACT

202-476-6022; JNazarian@cnmc.org

Caroline Kopsidas, BS

CONTACT

240-393-3359; ckopsidas@childrensnational.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 19, 2010
• First Posted: April 20, 2010
• Study Start: April 1, 2010
• Primary Completion: April 1, 2025
• Study Completion (Estimated): April 1, 2030
• Last Updated: August 20, 2024

Record last verified: 2024-08

Locations

US (1)