Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity
Autor: | Alexander Younsi, David E. Reuss, Johannes Kahn, David Capper, Anne Schöler, Georgios Ntoulias, Daniel Teichmann, Hee-Yeong Kim, Dag Moskopp, Diaa Al Safatli, Abigail K. Suwala, Jan Walter, Sven-Axel May, Peter Vajkoczy, David Kaul, Bettina Knie, Frank L. Heppner, Wolfgang Hartmann, Andreas Unterberg, Martin Hasselblatt, Leonille Schweizer, Damian Stichel, Felix Thierfelder, Christian Hartmann, Andreas Jödicke, Arend Koch, Martin Misch, Ruben Jödicke, Annika K. Wefers, Patrick Soschinski, Andreas von Deimling, Michael Bockmayr, Lars Wessels, Christian Thomas |
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Rok vydání: | 2020 |
Předmět: |
Male
musculoskeletal diseases Pathology medicine.medical_specialty genetics [Central Nervous System Neoplasms] genetics [Paraganglioma] SDHB diagnosis [Neoplasm Recurrence Local] Neuroendocrine tumors Biology Cauda equina Pathology and Forensic Medicine Central Nervous System Neoplasms Diagnosis Differential Paraganglioma Head and neck Cellular and Molecular Neuroscience Cytokeratin genetics [Neuroendocrine Tumors] Germline mutation pathology [Cauda Equina] pathology [Neuroendocrine Tumors] GATA3 medicine Humans ddc:610 pathology [Neoplasm Recurrence Local] diagnosis [Neuroendocrine Tumors] Germ-Line Mutation Exome sequencing genetics [Germ-Line Mutation] Original Paper DNA methylation Adrenal gland pathology [Central Nervous System Neoplasms] Prognosis medicine.disease genetics [Neoplasm Recurrence Local] pathology [Paraganglioma] Neuroendocrine Tumors medicine.anatomical_structure Female Neurology (clinical) Neoplasm Recurrence Local 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit |
Zdroj: | Acta neuropathologica 140(6), 893-906 (2020). doi:10.1007/s00401-020-02218-7 Acta Neuropathologica |
ISSN: | 1432-0533 0001-6322 |
Popis: | Paragangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular profiling of abdomino-thoracic paragangliomas revealed four molecularly defined and clinically relevant subtypes. Paragangliomas of the cauda equina region are considered to belong to one of the defined molecular subtypes, but a systematic molecular analysis has not yet been performed. In this study, we analyzed genome-wide DNA methylation profiles of 57 cauda equina paragangliomas and show that these tumors are epigenetically distinct from non-spinal paragangliomas and other tumors. In contrast to paragangliomas of other sites, chromosomal imbalances are widely lacking in cauda equina paragangliomas. Furthermore, RNA and DNA exome sequencing revealed that frequent genetic alterations found in non-spinal paragangliomas—including the prognostically relevant SDH mutations—are absent in cauda equina paragangliomas. Histologically, cauda equina paragangliomas show frequently gangliocytic differentiation and strong immunoreactivity to pan-cytokeratin and cytokeratin 18, which is not common in paragangliomas of other sites. None of our cases had a familial paraganglioma syndrome. Tumors rarely recurred (9%) or presented with multiple lesions within the spinal compartment (7%), but did not metastasize outside the CNS. In summary, we show that cauda equina paragangliomas represent a distinct, sporadic tumor entity defined by a unique clinical and morpho-molecular profile. Electronic supplementary material The online version of this article (10.1007/s00401-020-02218-7) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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