Molecular pathological insights reveal a high number of unfavorable risk patients among children treated for medulloblastoma and CNS-PNET in Oslo 2005-2017

Pitt Niehusmann; Einar Stensvold; Henning Leske; Torsten Pietsch; Tobias Goschzik; Gerrit H Gielen; Bernt Due-Tønnessen; Radek Frič; Yngvar Nilssen; Petter Brandal

doi:10.1002/pbc.29736

Molecular pathological insights reveal a high number of unfavorable risk patients among children treated for medulloblastoma and CNS-PNET in Oslo 2005-2017

Pediatr Blood Cancer. 2022 Sep;69(9):e29736. doi: 10.1002/pbc.29736. Epub 2022 May 15.

Authors

Pitt Niehusmann^{1

2}, Einar Stensvold³, Henning Leske^{1

2}, Torsten Pietsch⁴, Tobias Goschzik⁴, Gerrit H Gielen⁴, Bernt Due-Tønnessen⁵, Radek Frič⁵, Yngvar Nilssen⁶, Petter Brandal⁷

Affiliations

¹ Department of Neurology/Pathology, Oslo University Hospital, Oslo, Norway.
² Faculty of Medicine, Institute of Clinical Medicine (KlinMED), University of Oslo, Oslo, Norway.
³ Department of Pediatrics, Oslo University Hospital, Oslo, Norway.
⁴ Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn Medical Center, Bonn, Germany.
⁵ Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
⁶ Department of Registration, Cancer Registry of Norway, Oslo, Norway.
⁷ Department of Oncology, Oslo University Hospital, Oslo, Norway.

PMID: 35570402
DOI: 10.1002/pbc.29736

Abstract

Background: An unexplained regional difference in survival was observed in previous publications on outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. We aimed now to reevaluate and perform a retrospective molecular-based risk stratification of all embryonal brain tumors (excluding atypical teratoid rhabdoid tumors [ATRT]) in pediatric patients, who underwent surgery and treatment at Oslo University Hospital between 2005 and 2017.

Procedure: Specimens from all patients <20 years of age with initial diagnosis of medulloblastoma or CNS-PNET were reviewed. Molecular analyses comprised NanoString gene expression, molecular inversion probe profiling, Sanger sequencing, and 850K-methylation analysis. Whole chromosomal aberration signatures were assessed in standard-risk non-WNT/non-SHH medullobastomas for molecular risk stratification.

Results: We identified 53 non-ATRT embryonal tumors among which 33 were medulloblastomas. Molecular genetic parameters including whole chromosomal aberration signatures allowed classification of 17 medulloblastomas as molecular high risk. These patients had a significantly worse 5-year overall survival than the remaining 16 medulloblastoma patients (52.9% vs. 87.1% p = 0.036). Five patients in our cohort had tumors that are considered as new entities in the 2021 classification of tumors of the central nervous system. Five tumors were re-classified as nonembryonal tumors after review.

Conclusion: Molecular-based risk stratification of standard-risk non-WNT/non-SHH medulloblastoma enabled superior identification of medulloblastomas with dismal prognosis. Our cohort demonstrated a significantly increased fraction of standard-risk non-WNT/non-SHH medulloblastoma with molecular high-risk profile compared to other studies, which might have contributed to previously reported unfavorable outcome data.

Keywords: BCOR; CNS neuroblastoma; Norway; PATZ1; medulloblastoma; molecular pathology; risk stratification.

MeSH terms

Brain Neoplasms* / pathology
Central Nervous System Neoplasms* / genetics
Central Nervous System Neoplasms* / therapy
Cerebellar Neoplasms* / genetics
Cerebellar Neoplasms* / metabolism
Cerebellar Neoplasms* / therapy
Child
Chromosome Aberrations
Humans
Medulloblastoma* / genetics
Medulloblastoma* / metabolism
Medulloblastoma* / therapy
Neuroectodermal Tumors, Primitive* / pathology
Retrospective Studies
Rhabdoid Tumor* / genetics