eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
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vol. 57
Original paper

Hedgehog signalling network gene status analysis in paediatric intracranial germ cell tumours

Dominika Kuleszo
Beata Lipska-Ziętkiewicz
Magdalena Koczkowska
Krzysztof Zakrzewski
Wiesława Grajkowska
Marcin Roszkowski
Bożenna Dembowska-Bagińska
Katarzyna Czarnota
Elżbieta Adamkiewicz-Drożyńska
Ewa Iżycka-Świeszewska

Folia Neuropathol 2019; 57 (3): 227-238
Online publish date: 2019/09/30
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Germ cell tumours (GCTs) in the children comprise a group of tumours that originate from primordial germ cells but their pathogenesis is not clear. Intracranial GCTs represent a special subset of these paediatric neoplasms. Hedgehog (Hh) pathway gene status in GCTs is generally unexplored, while Hh signalling is involved in germ cell biology.

Material and methods
Comparative genomic profiling analysis with a microarray-comparative genomic hybridization (CGH) + single nucleotide polymorphism (SNP) technique in a group of intracranial paediatric GCTs was performed. The analysis included evaluation of genes being ligands, receptors, regulators, effectors, and targets of Hh signalling.

Chromosomal aberrations were found in 62% of examined tumours, showing their heterogeneity. A number of private genomic imbalances were observed, but only a few recurrent ones. The most common numerical changes were trisomies 19, 21 and monosomies 13, 18 while the most frequent structural aberration was gain/amplification of the chromosome 12p. The analysis of the gene status of Hh network elements showed imbalances in a proportion of tumours. PTCH1, GLI2, IHH and ZIC2 gene aberrations occurred most frequently. Moreover, six tumours had various copy gains or losses of several other genes involved in the pathway, including HHIP, GLI1, GLI3, DHH, SHH, SMO, PTCH2, and several genes from the WNT group. Interestingly, four cases showed losses of pathway repressors, with parallel gains of activators in two of them. Correlations with patho-clinical tumour features were not found, most probably due to the heterogeneity of the examined limited group.

Our results show few genomic alterations related to the Hh signalling pathway genes in paediatric intracranial GCTs. Further analysis of Hedgehog pathway alterations can potentially disclose its biological significance and define new prognostic factors and/or therapeutic targets for high-risk patients.


genomic imbalances, intracranial germ-cell tumours, PTCH1, Hedgehog signalling, ZIC2

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