Molecular characterisation of sporadic endolymphatic sac tumours and comparison to von Hippel–Lindau disease‐related tumours
| Autor: | Hee-Yeong Kim, Simone Schmid, Alexandra Förster, Patrick Soschinski, Daniel Teichmann, David E. Reuss, Ruben Jödicke, Ulrich-Wilhelm Thomale, Marcos Tatagiba, Christin Siewert, Julia Onken, Katharina Klein, Frank L. Heppner, Felix Thierfelder, Maximilian Nunninger, Andreas von Deimling, Niklas Woltering, David A. Solomon, Christian Hartmann, Arend Koch, Jens Schittenhelm, Leonille Schweizer, Helmut Mühleisen, Ori Staszewski, David Capper, Christian Thomas |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
pathology [von Hippel-Lindau Disease] von Hippel-Lindau Disease endocrine system diseases metabolism [Tumor Suppressor Proteins] urologic and male genital diseases Loss of heterozygosity 0302 clinical medicine genetics [von Hippel-Lindau Disease] TERT promoter mutation DNA methylation Middle Aged female genital diseases and pregnancy complications Exact test medicine.anatomical_structure Neurology 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit Adult Risk Histology pathology [Ear Neoplasms] genetics [Mutation] Biology pathology [Endolymphatic Sac] Endolymphatic sac Pathology and Forensic Medicine 03 medical and health sciences genetics [Tumor Suppressor Proteins] VHL Physiology (medical) medicine Humans ddc:610 genetics [Ear Neoplasms] Epigenetics Von Hippel–Lindau disease complications [Ear Neoplasms] neoplasms Ear Neoplasms endolymphatic sac tumour Tumor Suppressor Proteins Chromosome von Hippel-Lindau disease medicine.disease 030104 developmental biology complications [von Hippel-Lindau Disease] Chromosome 3 metabolism [Endolymphatic Sac] Mutation Cancer research Neurology (clinical) Endolymphatic Sac 030217 neurology & neurosurgery |
| Zdroj: | Neuropathology & applied neurobiology 47(6), 756-767 (2021). doi:10.1111/nan.12741 |
| ISSN: | 1365-2990 0305-1846 |
| DOI: | 10.1111/nan.12741 |
| Popis: | Aims: Although inactivation of the von Hippel-Lindau gene (VHL) on chromosome 3p25 is considered to be the major cause of hereditary endolymphatic sac tumours (ELSTs), the genetic background of sporadic ELST is largely unknown. The aim of this study was to determine the prevalence of VHL mutations in sporadic ELSTs and compare their characteristics to VHL-disease-related tumours. Methods: Genetic and epigenetic alterations were compared between 11 sporadic and 11 VHL-disease-related ELSTs by targeted sequencing and DNA methylation analysis. Results: VHL mutations and small deletions detected by targeted deep sequencing were identified in 9/11 sporadic ELSTs (82%). No other cancer-related genetic pathway was altered except for TERT promoter mutations in two sporadic ELST and one VHL-disease-related ELST (15%). Loss of heterozygosity of chromosome 3 was found in 6/10 (60%) VHL-disease-related and 10/11 (91%) sporadic ELSTs resulting in biallelic VHL inactivation in 8/10 (73%) sporadic ELSTs. DNA methylation profiling did not reveal differences between sporadic and VHL-disease-related ELSTs but reliably distinguished ELST from morphological mimics of the cerebellopontine angle. VHL patients were significantly younger at disease onset compared to sporadic ELSTs (29 vs. 52 years, p < 0.0001, Fisher's exact test). VHL-disease status was not associated with an increased risk of recurrence, but the presence of clear cells was found to be associated with shorter progression-free survival (p = 0.0002, log-rank test). Conclusion: Biallelic inactivation of VHL is the main mechanism underlying ELSTs, but unknown mechanisms beyond VHL may rarely be involved in the pathogenesis of sporadic ELSTs. |
| Databáze: | OpenAIRE |
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