Medulloblastoma therapy generates risk of a poorly-prognostic H3 wild-type subgroup of diffuse intrinsic pontine glioma: a report from the International DIPG Registry

With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry...

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Veröffentlicht in:	Acta neuropathologica communications Jg. 6; H. 1; S. 67 - 12
Hauptverfasser:	Gits, Hunter C., Anderson, Maia, Stallard, Stefanie, Pratt, Drew, Zon, Becky, Howell, Christopher, Kumar-Sinha, Chandan, Vats, Pankaj, Kasaian, Katayoon, Polan, Daniel, Matuszak, Martha, Spratt, Daniel E., Leonard, Marcia, Qin, Tingting, Zhao, Lili, Leach, James, Chaney, Brooklyn, Escorza, Nancy Yanez, Hendershot, Jacob, Jones, Blaise, Fuller, Christine, Leary, Sarah, Bartels, Ute, Bouffet, Eric, Yock, Torunn I., Robertson, Patricia, Mody, Rajen, Venneti, Sriram, Chinnaiyan, Arul M., Fouladi, Maryam, Gottardo, Nicholas G., Koschmann, Carl
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London BioMed Central 26.07.2018 BioMed Central Ltd Nature Publishing Group BMC
Schlagworte:	Biomedical and Life Sciences Biomedicine Brain cancer Brain tumors Brainstem Cancer therapies Care and treatment Cranial irradiation Diffuse intrinsic pontine glioma Epigenetic inheritance Epigenetics Glioma Medical prognosis Medulloblastoma Mutation Neurology Neurosciences Pathology Pediatrics Radiation (Physics) Radiation therapy Radiotherapy Secondary malignant neoplasm Studies Tumors Cranial irradiation Secondary malignant neoplasm Diffuse intrinsic pontine glioma Medulloblastoma Brainstem
ISSN:	2051-5960, 2051-5960
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Abstract	With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years). From these cases, molecular subgrouping of primary medulloblastomas with available tissue ( n = 5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). The estimated cumulative incidence of DIPG after post-treatment medulloblastoma ranged from 0.3–3.9%. Posterior fossa radiation exposure (including brainstem) was greater than 53.0 Gy in all cases with available details. Tumor/germline exome sequencing of three radiation-associated DIPGs revealed an H3 wild-type status and mutational signature distinct from primary DIPG with evidence of radiation-induced DNA damage. Mutations identified in the radiation-associated DIPGs had significant molecular overlap with recurrent drivers of adult glioblastoma (e.g. NRAS , EGFR , and PTEN ), as opposed to epigenetic dysregulation in H3-driven primary DIPGs. Patients with radiation-associated DIPG had a significantly worse median overall survival (median 8 months; range 4–17 months) compared to patients with primary DIPG. Here, it is demonstrated that DIPG occurs as a not infrequent complication of radiation therapy in survivors of pediatric medulloblastoma and that radiation-associated DIPGs may present as a poorly-prognostic distinct molecular subgroup of H3 wild-type DIPG. Given the abysmal survival of these cases, these findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma. Additionally, patients with radiation-associated DIPG may benefit from future therapies targeted to the molecular features of adult glioblastoma rather than primary DIPG.
AbstractList	With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years). From these cases, molecular subgrouping of primary medulloblastomas with available tissue ( n = 5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). The estimated cumulative incidence of DIPG after post-treatment medulloblastoma ranged from 0.3–3.9%. Posterior fossa radiation exposure (including brainstem) was greater than 53.0 Gy in all cases with available details. Tumor/germline exome sequencing of three radiation-associated DIPGs revealed an H3 wild-type status and mutational signature distinct from primary DIPG with evidence of radiation-induced DNA damage. Mutations identified in the radiation-associated DIPGs had significant molecular overlap with recurrent drivers of adult glioblastoma (e.g. NRAS , EGFR , and PTEN ), as opposed to epigenetic dysregulation in H3-driven primary DIPGs. Patients with radiation-associated DIPG had a significantly worse median overall survival (median 8 months; range 4–17 months) compared to patients with primary DIPG. Here, it is demonstrated that DIPG occurs as a not infrequent complication of radiation therapy in survivors of pediatric medulloblastoma and that radiation-associated DIPGs may present as a poorly-prognostic distinct molecular subgroup of H3 wild-type DIPG. Given the abysmal survival of these cases, these findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma. Additionally, patients with radiation-associated DIPG may benefit from future therapies targeted to the molecular features of adult glioblastoma rather than primary DIPG. With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years). From these cases, molecular subgrouping of primary medulloblastomas with available tissue (n = 5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). The estimated cumulative incidence of DIPG after post-treatment medulloblastoma ranged from 0.3-3.9%. Posterior fossa radiation exposure (including brainstem) was greater than 53.0 Gy in all cases with available details. Tumor/germline exome sequencing of three radiation-associated DIPGs revealed an H3 wild-type status and mutational signature distinct from primary DIPG with evidence of radiation-induced DNA damage. Mutations identified in the radiation-associated DIPGs had significant molecular overlap with recurrent drivers of adult glioblastoma (e.g. NRAS, EGFR, and PTEN), as opposed to epigenetic dysregulation in H3-driven primary DIPGs. Patients with radiation-associated DIPG had a significantly worse median overall survival (median 8 months; range 4-17 months) compared to patients with primary DIPG. Here, it is demonstrated that DIPG occurs as a not infrequent complication of radiation therapy in survivors of pediatric medulloblastoma and that radiation-associated DIPGs may present as a poorly-prognostic distinct molecular subgroup of H3 wild-type DIPG. Given the abysmal survival of these cases, these findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma. Additionally, patients with radiation-associated DIPG may benefit from future therapies targeted to the molecular features of adult glioblastoma rather than primary DIPG. Keywords: Secondary malignant neoplasm, Diffuse intrinsic pontine glioma, Medulloblastoma, Cranial irradiation, Brainstem With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years). From these cases, molecular subgrouping of primary medulloblastomas with available tissue (n = 5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). The estimated cumulative incidence of DIPG after post-treatment medulloblastoma ranged from 0.3-3.9%. Posterior fossa radiation exposure (including brainstem) was greater than 53.0 Gy in all cases with available details. Tumor/germline exome sequencing of three radiation-associated DIPGs revealed an H3 wild-type status and mutational signature distinct from primary DIPG with evidence of radiation-induced DNA damage. Mutations identified in the radiation-associated DIPGs had significant molecular overlap with recurrent drivers of adult glioblastoma (e.g. NRAS, EGFR, and PTEN), as opposed to epigenetic dysregulation in H3-driven primary DIPGs. Patients with radiation-associated DIPG had a significantly worse median overall survival (median 8 months; range 4-17 months) compared to patients with primary DIPG. Here, it is demonstrated that DIPG occurs as a not infrequent complication of radiation therapy in survivors of pediatric medulloblastoma and that radiation-associated DIPGs may present as a poorly-prognostic distinct molecular subgroup of H3 wild-type DIPG. Given the abysmal survival of these cases, these findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma. Additionally, patients with radiation-associated DIPG may benefit from future therapies targeted to the molecular features of adult glioblastoma rather than primary DIPG. Table 2 Characteristics of survivors of pediatric medulloblastoma who developed radiation-associated DIPG Primary Medulloblastoma Radiation-associated DIPG Case number - location Age at diagnosis (years) Gender Risk stratification Histology, subgroup Time in remission (years) Age at diagnosis (years) Treatment Histology (sequencing) Outcome (months after DIPG diagnosis) 1 - IDIPGR (Michigan Medicine) 8 F Average Classic, Group 4 (isochromosome 17q) 12 21 54 Gy focal radiation treatment, panobinostat High-grade glioma (TP53 loss, PTEN loss, NRAS mutation) Died of disease (17) 2 - IDIPGR (Michigan Medicine) 9 M Average Classic, Group 3/4 7 16 Patient declined Biopsy deferred Died of disease (4) 3 - IDIPGR (Michigan Medicine) 4 M High Classic, Group 3 4 9 35 Gy focal radiation treatment, everolimus High-grade glioma (PIK3CA and EZH2 mutations) Living (5) 4 - IDIPGR (Hospital for Sick Children) 2 M High Classic, Group 3 2 7 Etoposide, temozolomide, mechlorethamine, cyclophosphamide Not reported Died of disease (5) 5 - IDIPGR (Seattle Children’s Hospital) 6 M Average Classic, Group 4 10 17 Temozolomide Not biopsied; diagnosis made by imaging Died of disease (10) 6 - IDIPGR (Princess Margaret Hospital for Children) 4 M High Classic, Group 4 11 15 Focal radiation treatment, vorinostat High-grade glioma (PIK3CA mutation) Died of disease (8) 7- Packer et al. 2013 [31] (COG A9961) 3–21 Not reported Average Not reported 6.5 Not reported Not reported Pilocytic astrocytomaa Died of disease (10) 8 - Packer et al. 2013 [31] (COG A9961) 3–21 Not reported Average Not reported 9 Not reported Not reported Biopsy deferred Not reported 9 - Von Hoff et al. 2009 [42] (HIT’91) 3–18 Not reported Not reported Not reported Not reported Not reported Not reported Not reported Not reported 10 - Sabel et al. 2016 [36] (HIT-SIOP-PNET4) 4–21 Not reported Average Not reported 5.1 Not reported Not reported Anaplastic astrocytoma Died of disease (Not reported) 11 - Packer et al. 1999 [30] (CCG 9892) 3–10 Not reported Average Not reported 4.8 Not reported Not reported Glioma, grade unspecified Died of disease (Not reported) 12 - You et al. 2013 [46] (Yonsei Hospital) 8 M Not reported Not reported 7.8 Not reported Temozolomide Anaplastic astrocytoma Died of disease (6) aPathology was not reviewed centrally by trial Treatment details are described in Additional file 1: The brainstem is contoured in purple and received a mean dose of 50.1 Gy. c MR axial T2 FLAIR image of DIPG diagnosed at age 21, 13 years after treatment for primary medulloblastoma and in the area of the previously irradiated field. d MR spectroscopy with an elevated Chol/Cr ratio (1.66) that is consistent with malignancy (DIPG) Fig. 3 Fig. 3 Histology and molecular results distinguish primary medulloblastoma from radiation-associated DIPG. a Resected medulloblastoma from case 1 showing characteristic classic-type features including sheets of cells with primitive hyperchromatic nuclei and scant cytoplasm. b DIPG at autopsy showing an infiltrating glial tumor with small angulated nuclei and abundant amphophilic cytoplasm. c Karyotype analysis of medulloblastoma shows near-tetraploid clone with arrow indicating i(17q), most consistent with Group 4. d Copy number analysis of DIPG shows focal and structural changes distinct from primary tumor, including focal homozygous loss of RB1, SETDB2, CDKN2A and CDKN2B, focal 1 copy gain of KIT, KDR and PDGFRA, and activation mutations in NRAS and TP53. e Loss of heterozygosity plot showing regions on chromosomes 6 and 18 with copy-neutral loss of heterozygosity events DIPG sequencing For cases 1, 3, and 6, DIPG frozen tissue from autopsy (cases 1 and 6) and diagnosis (case 3) were sequenced and mutations were analyzed (Additional file 1: Notably, sequencing confirmed that the tumors were indeed distinct from their primary malignancies and not local recurrences. [...]patients did not harbor germline mutations in known cancer predisposition genes. (DOCX 5366 kb) Authors’ Affiliations (1) Department of Pathology, Michigan Medicine, Ann Arbor, MI 48109, USA (2) Department of Pediatrics, Division of Pediatric Hematology-Oncology; Michigan Medicine, Ann Arbor, MI 48109, USA (3) Department of Haematology and Oncology, Princess Margaret Hospital for Children, Perth, WA, 6840, Australia (4) Michigan Center for Translational Pathology, Michigan Medicine, Ann Arbor, MI 48109, USA (5) Ontario Institute for Cancer Research, MG5 0A3, Toronto, ON, Canada (6) Department of Radiation Oncology; Michigan Medicine, Ann Arbor, MI 48109, USA (7) Department of Computational Medicine and Bioinformatics; Michigan Medicine, Ann Arbor, MI 48109, USA (8) Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA (9) Division of Radiology, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USA (10) Division of Oncology, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USA (11) Division of Biomedical Informatics, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USA (12) Division of Pathology, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USA (13) Department of Pediatrics, Division of Oncology, Seattle Children’s Hospital, Seattle, WA 98105, USA (14) Department of Pediatrics, Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada (15) Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA (16) Department of Pediatrics, Division of Neurology; Michigan Medicine, Ann Arbor, MI 48109, USA (17) Department of Pediatrics, Division of Oncology, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USA (18) Kids Cancer Centre, Telethon Kids Institute, Subiaco, WA, 6008, Australia (19) Division of Paediatrics, University of Western Australia, Crawley, WA, 6009, Australia Abboud SE, Wolansky LJ, Manjila SV, Lo SS, Arafah BM, Selman WR, Couce ME, Rogers LR (2015) Histologically proven radiation-induced brainstem Glioma 93 months after external beam radiotherapy for pituitary macroadenoma: radiation treatment dose and volume correlation. With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years). From these cases, molecular subgrouping of primary medulloblastomas with available tissue (n = 5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). The estimated cumulative incidence of DIPG after post-treatment medulloblastoma ranged from 0.3-3.9%. Posterior fossa radiation exposure (including brainstem) was greater than 53.0 Gy in all cases with available details. Tumor/germline exome sequencing of three radiation-associated DIPGs revealed an H3 wild-type status and mutational signature distinct from primary DIPG with evidence of radiation-induced DNA damage. Mutations identified in the radiation-associated DIPGs had significant molecular overlap with recurrent drivers of adult glioblastoma (e.g. NRAS, EGFR, and PTEN), as opposed to epigenetic dysregulation in H3-driven primary DIPGs. Patients with radiation-associated DIPG had a significantly worse median overall survival (median 8 months; range 4-17 months) compared to patients with primary DIPG. Here, it is demonstrated that DIPG occurs as a not infrequent complication of radiation therapy in survivors of pediatric medulloblastoma and that radiation-associated DIPGs may present as a poorly-prognostic distinct molecular subgroup of H3 wild-type DIPG. Given the abysmal survival of these cases, these findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma. Additionally, patients with radiation-associated DIPG may benefit from future therapies targeted to the molecular features of adult glioblastoma rather than primary DIPG.With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years). From these cases, molecular subgrouping of primary medulloblastomas with available tissue (n = 5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). The estimated cumulative incidence of DIPG after post-treatment medulloblastoma ranged from 0.3-3.9%. Posterior fossa radiation exposure (including brainstem) was greater than 53.0 Gy in all cases with available details. Tumor/germline exome sequencing of three radiation-associated DIPGs revealed an H3 wild-type status and mutational signature distinct from primary DIPG with evidence of radiation-induced DNA damage. Mutations identified in the radiation-associated DIPGs had significant molecular overlap with recurrent drivers of adult glioblastoma (e.g. NRAS, EGFR, and PTEN), as opposed to epigenetic dysregulation in H3-driven primary DIPGs. Patients with radiation-associated DIPG had a significantly worse median overall survival (median 8 months; range 4-17 months) compared to patients with primary DIPG. Here, it is demonstrated that DIPG occurs as a not infrequent complication of radiation therapy in survivors of pediatric medulloblastoma and that radiation-associated DIPGs may present as a poorly-prognostic distinct molecular subgroup of H3 wild-type DIPG. Given the abysmal survival of these cases, these findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma. Additionally, patients with radiation-associated DIPG may benefit from future therapies targeted to the molecular features of adult glioblastoma rather than primary DIPG. Abstract With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years). From these cases, molecular subgrouping of primary medulloblastomas with available tissue (n = 5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). The estimated cumulative incidence of DIPG after post-treatment medulloblastoma ranged from 0.3–3.9%. Posterior fossa radiation exposure (including brainstem) was greater than 53.0 Gy in all cases with available details. Tumor/germline exome sequencing of three radiation-associated DIPGs revealed an H3 wild-type status and mutational signature distinct from primary DIPG with evidence of radiation-induced DNA damage. Mutations identified in the radiation-associated DIPGs had significant molecular overlap with recurrent drivers of adult glioblastoma (e.g. NRAS, EGFR, and PTEN), as opposed to epigenetic dysregulation in H3-driven primary DIPGs. Patients with radiation-associated DIPG had a significantly worse median overall survival (median 8 months; range 4–17 months) compared to patients with primary DIPG. Here, it is demonstrated that DIPG occurs as a not infrequent complication of radiation therapy in survivors of pediatric medulloblastoma and that radiation-associated DIPGs may present as a poorly-prognostic distinct molecular subgroup of H3 wild-type DIPG. Given the abysmal survival of these cases, these findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma. Additionally, patients with radiation-associated DIPG may benefit from future therapies targeted to the molecular features of adult glioblastoma rather than primary DIPG. With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years). From these cases, molecular subgrouping of primary medulloblastomas with available tissue (n = 5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). The estimated cumulative incidence of DIPG after post-treatment medulloblastoma ranged from 0.3-3.9%. Posterior fossa radiation exposure (including brainstem) was greater than 53.0 Gy in all cases with available details. Tumor/germline exome sequencing of three radiation-associated DIPGs revealed an H3 wild-type status and mutational signature distinct from primary DIPG with evidence of radiation-induced DNA damage. Mutations identified in the radiation-associated DIPGs had significant molecular overlap with recurrent drivers of adult glioblastoma (e.g. NRAS, EGFR, and PTEN), as opposed to epigenetic dysregulation in H3-driven primary DIPGs. Patients with radiation-associated DIPG had a significantly worse median overall survival (median 8 months; range 4-17 months) compared to patients with primary DIPG. Here, it is demonstrated that DIPG occurs as a not infrequent complication of radiation therapy in survivors of pediatric medulloblastoma and that radiation-associated DIPGs may present as a poorly-prognostic distinct molecular subgroup of H3 wild-type DIPG. Given the abysmal survival of these cases, these findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma. Additionally, patients with radiation-associated DIPG may benefit from future therapies targeted to the molecular features of adult glioblastoma rather than primary DIPG.
ArticleNumber	67
Audience	Academic
Author	Leonard, Marcia Kasaian, Katayoon Zhao, Lili Bouffet, Eric Qin, Tingting Robertson, Patricia Mody, Rajen Koschmann, Carl Fouladi, Maryam Anderson, Maia Vats, Pankaj Stallard, Stefanie Escorza, Nancy Yanez Bartels, Ute Kumar-Sinha, Chandan Matuszak, Martha Leach, James Yock, Torunn I. Chaney, Brooklyn Hendershot, Jacob Gits, Hunter C. Howell, Christopher Spratt, Daniel E. Jones, Blaise Chinnaiyan, Arul M. Polan, Daniel Venneti, Sriram Leary, Sarah Fuller, Christine Zon, Becky Gottardo, Nicholas G. Pratt, Drew
Author_xml	– sequence: 1 givenname: Hunter C. surname: Gits fullname: Gits, Hunter C. organization: Department of Pediatrics, Division of Pediatric Hematology-Oncology; Michigan Medicine – sequence: 2 givenname: Maia surname: Anderson fullname: Anderson, Maia organization: Department of Pediatrics, Division of Pediatric Hematology-Oncology; Michigan Medicine – sequence: 3 givenname: Stefanie surname: Stallard fullname: Stallard, Stefanie organization: Department of Pediatrics, Division of Pediatric Hematology-Oncology; Michigan Medicine – sequence: 4 givenname: Drew surname: Pratt fullname: Pratt, Drew organization: Department of Pathology, Michigan Medicine – sequence: 5 givenname: Becky surname: Zon fullname: Zon, Becky organization: Department of Pediatrics, Division of Pediatric Hematology-Oncology; Michigan Medicine – sequence: 6 givenname: Christopher surname: Howell fullname: Howell, Christopher organization: Department of Haematology and Oncology, Princess Margaret Hospital for Children – sequence: 7 givenname: Chandan surname: Kumar-Sinha fullname: Kumar-Sinha, Chandan organization: Department of Pathology, Michigan Medicine, Michigan Center for Translational Pathology, Michigan Medicine – sequence: 8 givenname: Pankaj surname: Vats fullname: Vats, Pankaj organization: Department of Pathology, Michigan Medicine, Michigan Center for Translational Pathology, Michigan Medicine – sequence: 9 givenname: Katayoon surname: Kasaian fullname: Kasaian, Katayoon organization: Ontario Institute for Cancer Research – sequence: 10 givenname: Daniel surname: Polan fullname: Polan, Daniel organization: Department of Radiation Oncology; Michigan Medicine – sequence: 11 givenname: Martha surname: Matuszak fullname: Matuszak, Martha organization: Department of Radiation Oncology; Michigan Medicine – sequence: 12 givenname: Daniel E. surname: Spratt fullname: Spratt, Daniel E. organization: Department of Radiation Oncology; Michigan Medicine – sequence: 13 givenname: Marcia surname: Leonard fullname: Leonard, Marcia organization: Department of Pediatrics, Division of Pediatric Hematology-Oncology; Michigan Medicine – sequence: 14 givenname: Tingting surname: Qin fullname: Qin, Tingting organization: Department of Computational Medicine and Bioinformatics; Michigan Medicine – sequence: 15 givenname: Lili surname: Zhao fullname: Zhao, Lili organization: Department of Biostatistics, University of Michigan School of Public Health – sequence: 16 givenname: James surname: Leach fullname: Leach, James organization: Division of Radiology, Cincinnati Children’s Hospital – sequence: 17 givenname: Brooklyn surname: Chaney fullname: Chaney, Brooklyn organization: Division of Oncology, Cincinnati Children’s Hospital – sequence: 18 givenname: Nancy Yanez surname: Escorza fullname: Escorza, Nancy Yanez organization: Division of Oncology, Cincinnati Children’s Hospital – sequence: 19 givenname: Jacob surname: Hendershot fullname: Hendershot, Jacob organization: Division of Biomedical Informatics, Cincinnati Children’s Hospital – sequence: 20 givenname: Blaise surname: Jones fullname: Jones, Blaise organization: Division of Radiology, Cincinnati Children’s Hospital – sequence: 21 givenname: Christine surname: Fuller fullname: Fuller, Christine organization: Division of Pathology, Cincinnati Children’s Hospital – sequence: 22 givenname: Sarah surname: Leary fullname: Leary, Sarah organization: Department of Pediatrics, Division of Oncology, Seattle Children’s Hospital – sequence: 23 givenname: Ute surname: Bartels fullname: Bartels, Ute organization: Department of Pediatrics, Division of Haematology/Oncology, Hospital for Sick Children – sequence: 24 givenname: Eric surname: Bouffet fullname: Bouffet, Eric organization: Department of Pediatrics, Division of Haematology/Oncology, Hospital for Sick Children – sequence: 25 givenname: Torunn I. surname: Yock fullname: Yock, Torunn I. organization: Department of Radiation Oncology, Massachusetts General Hospital – sequence: 26 givenname: Patricia surname: Robertson fullname: Robertson, Patricia organization: Department of Pediatrics, Division of Neurology; Michigan Medicine – sequence: 27 givenname: Rajen surname: Mody fullname: Mody, Rajen organization: Department of Pediatrics, Division of Pediatric Hematology-Oncology; Michigan Medicine – sequence: 28 givenname: Sriram surname: Venneti fullname: Venneti, Sriram organization: Department of Pathology, Michigan Medicine – sequence: 29 givenname: Arul M. surname: Chinnaiyan fullname: Chinnaiyan, Arul M. organization: Department of Pathology, Michigan Medicine, Michigan Center for Translational Pathology, Michigan Medicine – sequence: 30 givenname: Maryam surname: Fouladi fullname: Fouladi, Maryam organization: Department of Pediatrics, Division of Oncology, Cincinnati Children’s Hospital – sequence: 31 givenname: Nicholas G. surname: Gottardo fullname: Gottardo, Nicholas G. organization: Michigan Center for Translational Pathology, Michigan Medicine, Kids Cancer Centre, Telethon Kids Institute, Division of Paediatrics, University of Western Australia – sequence: 32 givenname: Carl orcidid: 0000-0002-0825-7615 surname: Koschmann fullname: Koschmann, Carl email: ckoschma@med.umich.edu organization: Department of Pediatrics, Division of Pediatric Hematology-Oncology; Michigan Medicine
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/30049282$$D View this record in MEDLINE/PubMed
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Snippet	With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed... Table 2 Characteristics of survivors of pediatric medulloblastoma who developed radiation-associated DIPG Primary Medulloblastoma Radiation-associated DIPG... Abstract With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically...
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SubjectTerms	Biomedical and Life Sciences Biomedicine Brain cancer Brain tumors Brainstem Cancer therapies Care and treatment Cranial irradiation Diffuse intrinsic pontine glioma Epigenetic inheritance Epigenetics Glioma Medical prognosis Medulloblastoma Mutation Neurology Neurosciences Pathology Pediatrics Radiation (Physics) Radiation therapy Radiotherapy Secondary malignant neoplasm Studies Tumors
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Title	Medulloblastoma therapy generates risk of a poorly-prognostic H3 wild-type subgroup of diffuse intrinsic pontine glioma: a report from the International DIPG Registry
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