Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Redefining germline predisposition in children with molecularly characterized ependymoma: a population-based 20-year cohort

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Altered lipid metabolism marks glioblastoma stem and non-stem cells in separate tumor niches

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Autophagy is affected in patients with hypokalemic periodic paralysis: an involvement in vacuolar myopathy?

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Exploration of the induced cytokine responses in European Lyme neuroborreliosis: A longitudinal cohort study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Changes in body mass index during treatment of childhood acute lymphoblastic leukemia with the Nordic ALL2008 protocol

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Modeling of waning immunity after SARS-CoV-2 vaccination and influencing factors

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Genetic predisposition to central nervous system tumors in children - what the neurosurgeon should know

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

Vis graf over relationer

Ependymoma is the second most common malignant brain tumor in children. The etiology is largely unknown and germline DNA sequencing studies focusing on childhood ependymoma are limited. We therefore performed germline whole-genome sequencing on a population-based cohort of children diagnosed with ependymoma in Denmark over the past 20 years (n = 43). Single nucleotide and structural germline variants in 457 cancer related genes and 2986 highly evolutionarily constrained genes were assessed in 37 children with normal tissue available for sequencing. Molecular ependymoma classification was performed using DNA methylation profiling for 39 children with available tumor tissue. Pathogenic germline variants in known cancer predisposition genes were detected in 11% (4/37; NF2, LZTR1, NF1 & TP53). However, DNA methylation profiling resulted in revision of the histopathological ependymoma diagnosis to non-ependymoma tumor types in 8% (3/39). This included the two children with pathogenic germline variants in TP53 and NF1 whose tumors were reclassified to a diffuse midline glioma and a rosette-forming glioneuronal tumor, respectively. Consequently, 50% (2/4) of children with pathogenic germline variants in fact had other tumor types. A meta-analysis combining our findings with pediatric pan-cancer germline sequencing studies showed an overall frequency of pathogenic germline variants of 3.4% (7/207) in children with ependymoma. In summary, less than 4% of childhood ependymoma is explained by genetic predisposition, virtually restricted to pathogenic variants in NF2 and NF1. For children with other cancer predisposition syndromes, diagnostic reconsideration is recommended for ependymomas without molecular classification. Additionally, LZTR1 is suggested as a novel putative ependymoma predisposition gene.

OriginalsprogEngelsk
Artikelnummer123
TidsskriftActa neuropathologica communications
Vol/bind10
Udgave nummer1
Sider (fra-til)123
ISSN2051-5960
DOI
StatusUdgivet - 25 aug. 2022

Bibliografisk note

© 2022. The Author(s).

ID: 80462116