Novel paediatric case of a spinal high-grade astrocytoma with piloid features in a patient with Noonan Syndrome
Noonan Syndrome (NS) is associated with an increased risk of low-grade central nervous system tumours in children but only very rarely associated with high-grade gliomas. Here we describe the first reported case of a spinal high-grade astrocytoma with piloid features (HGAP) in a child with NS. This case was a diagnostic and treatment dilemma, prior to whole-genome germline and tumour sequencing, tumour transcriptome sequencing and DNA methylation analysis. The methylation profile matched strongly with HGAP and sequencing identified somatic FGFR1 and NF1 variants and a PTPN11 germline pathogenic variant. Therapeutic targets were identified but also alterations novel to HGAP such as differential expression of VEGFA and PD-L1. The germline PTPN11 finding has not been previously described in individuals with HGAP. This case underscores the power of precision medicine from a diagnostic, therapeutic and clinical management perspective, and describes an association between HGAP and NS which has not previously been reported.
Authors
- Pamela Ajuyah (ORCID: https://orcid.org/0000-0002-5529-1461)
- Neevika Manoharan (ORCID: https://orcid.org/0000-0002-2914-8637)
- Noemi Fuentes-Bolanos
- Paulette Barahona (ORCID: https://orcid.org/0000-0002-3184-8499)
- Marie Wong (ORCID: https://orcid.org/0000-0003-0066-6606)
- Angela Harris
- David S. Ziegler (ORCID: https://orcid.org/0000-0001-7451-7916)
- Chelsea Mayoh (ORCID: https://orcid.org/0000-0002-6398-3046)
- Loretta M. S. Lau (ORCID: https://orcid.org/0000-0002-3172-0970)
- Patricia J. Sullivan
- Megan Rumford (ORCID: https://orcid.org/0000-0001-7480-9273)
- Mark J. Cowley (ORCID: https://orcid.org/0000-0002-9519-5714)
- Paul G. Ekert (ORCID: https://orcid.org/0000-0002-2976-8617)
- Jordan Staunton
Institutions
- New South Wales Department of Health (AU)
- Royal Children's Hospital (AU)
- The University of Melbourne (AU)
- Peter MacCallum Cancer Centre (AU)
- Cancer Institute of New South Wales (AU)
- UNSW Sydney (AU)
- Prince of Wales Hospital (AU)
- Sydney Children's Hospital (AU)
- Murdoch Children's Research Institute (AU)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2024-10-19
- DOI
- https://doi.org/10.1038/s41698-024-00734-3
- Citations
- 2
- Primary Topic
- Protein Tyrosine Phosphatases
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- Children's Hospital Foundation
- Australian Government
- Australian Cancer Research Foundation
- Cancer Australia
- Cancer Institute NSW
- University of New South Wales
- Cure Brain Cancer Foundation
- NSW Ministry of Health
- Minderoo Foundation
- Australian Genomics Health Alliance
- Kids Cancer Alliance
- Tour de Cure
- Medical Research Council
- National Health and Medical Research Council