Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity
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Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity. / Schweizer, Leonille; Thierfelder, Felix; Thomas, Christian; Soschinski, Patrick; Suwala, Abigail; Stichel, Damian; Wefers, Annika K; Wessels, Lars; Misch, Martin; Kim, Hee-Yeong; Jödicke, Ruben; Teichmann, Daniel; Kaul, David; Kahn, Johannes; Bockmayr, Michael; Hasselblatt, Martin; Younsi, Alexander; Unterberg, Andreas; Knie, Bettina; Walter, Jan; Al Safatli, Diaa; May, Sven-Axel; Jödicke, Andreas; Ntoulias, Georgios; Moskopp, Dag; Vajkoczy, Peter; Heppner, Frank L; Capper, David; Hartmann, Wolfgang; Hartmann, Christian; von Deimling, Andreas; Reuss, David E; Schöler, Anne; Koch, Arend.
in: ACTA NEUROPATHOL, Jahrgang 140, Nr. 6, 12.2020, S. 893-906.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity
AU - Schweizer, Leonille
AU - Thierfelder, Felix
AU - Thomas, Christian
AU - Soschinski, Patrick
AU - Suwala, Abigail
AU - Stichel, Damian
AU - Wefers, Annika K
AU - Wessels, Lars
AU - Misch, Martin
AU - Kim, Hee-Yeong
AU - Jödicke, Ruben
AU - Teichmann, Daniel
AU - Kaul, David
AU - Kahn, Johannes
AU - Bockmayr, Michael
AU - Hasselblatt, Martin
AU - Younsi, Alexander
AU - Unterberg, Andreas
AU - Knie, Bettina
AU - Walter, Jan
AU - Al Safatli, Diaa
AU - May, Sven-Axel
AU - Jödicke, Andreas
AU - Ntoulias, Georgios
AU - Moskopp, Dag
AU - Vajkoczy, Peter
AU - Heppner, Frank L
AU - Capper, David
AU - Hartmann, Wolfgang
AU - Hartmann, Christian
AU - von Deimling, Andreas
AU - Reuss, David E
AU - Schöler, Anne
AU - Koch, Arend
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
U2 - 10.1007/s00401-020-02218-7
DO - 10.1007/s00401-020-02218-7
M3 - SCORING: Journal article
C2 - 32926213
VL - 140
SP - 893
EP - 906
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 6
ER -