Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity
Abstract 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 mo...
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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Enthalten in: Acta neuropathologica - Berlin : Springer, 1961, 140(2020), 6 vom: 14. Sept., Seite 893-906 |
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| Übergeordnetes Werk: |
volume:140 ; year:2020 ; number:6 ; day:14 ; month:09 ; pages:893-906 |
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| DOI / URN: |
10.1007/s00401-020-02218-7 |
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| 100 | 1 | |a Schweizer, Leonille |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity |
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| 520 | |a Abstract 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. | ||
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10.1007/s00401-020-02218-7 doi (DE-627)SPR041979060 (SPR)s00401-020-02218-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.90 bkl Schweizer, Leonille verfasserin aut Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Paraganglioma (dpeaa)DE-He213 Cauda equina (dpeaa)DE-He213 Head and neck (dpeaa)DE-He213 SDHB (dpeaa)DE-He213 GATA3 (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Thierfelder, Felix verfasserin aut Thomas, Christian verfasserin aut Soschinski, Patrick verfasserin aut Suwala, Abigail verfasserin aut Stichel, Damian verfasserin aut Wefers, Annika K. verfasserin aut Wessels, Lars verfasserin aut Misch, Martin verfasserin aut Kim, Hee-yeong verfasserin aut Jödicke, Ruben verfasserin aut Teichmann, Daniel verfasserin aut Kaul, David verfasserin aut Kahn, Johannes verfasserin aut Bockmayr, Michael verfasserin aut Hasselblatt, Martin verfasserin aut Younsi, Alexander verfasserin aut Unterberg, Andreas verfasserin aut Knie, Bettina verfasserin aut Walter, Jan verfasserin aut Al Safatli, Diaa verfasserin aut May, Sven-Axel verfasserin aut Jödicke, Andreas verfasserin aut Ntoulias, Georgios verfasserin aut Moskopp, Dag verfasserin aut Vajkoczy, Peter verfasserin aut Heppner, Frank L. verfasserin aut Capper, David verfasserin aut Hartmann, Wolfgang verfasserin aut Hartmann, Christian verfasserin aut von Deimling, Andreas verfasserin aut Reuss, David E. verfasserin aut Schöler, Anne verfasserin aut Koch, Arend verfasserin aut Enthalten in Acta neuropathologica Berlin : Springer, 1961 140(2020), 6 vom: 14. Sept., Seite 893-906 (DE-627)253389666 (DE-600)1458410-4 1432-0533 nnns volume:140 year:2020 number:6 day:14 month:09 pages:893-906 https://dx.doi.org/10.1007/s00401-020-02218-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 140 2020 6 14 09 893-906 |
| spelling |
10.1007/s00401-020-02218-7 doi (DE-627)SPR041979060 (SPR)s00401-020-02218-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.90 bkl Schweizer, Leonille verfasserin aut Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Paraganglioma (dpeaa)DE-He213 Cauda equina (dpeaa)DE-He213 Head and neck (dpeaa)DE-He213 SDHB (dpeaa)DE-He213 GATA3 (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Thierfelder, Felix verfasserin aut Thomas, Christian verfasserin aut Soschinski, Patrick verfasserin aut Suwala, Abigail verfasserin aut Stichel, Damian verfasserin aut Wefers, Annika K. verfasserin aut Wessels, Lars verfasserin aut Misch, Martin verfasserin aut Kim, Hee-yeong verfasserin aut Jödicke, Ruben verfasserin aut Teichmann, Daniel verfasserin aut Kaul, David verfasserin aut Kahn, Johannes verfasserin aut Bockmayr, Michael verfasserin aut Hasselblatt, Martin verfasserin aut Younsi, Alexander verfasserin aut Unterberg, Andreas verfasserin aut Knie, Bettina verfasserin aut Walter, Jan verfasserin aut Al Safatli, Diaa verfasserin aut May, Sven-Axel verfasserin aut Jödicke, Andreas verfasserin aut Ntoulias, Georgios verfasserin aut Moskopp, Dag verfasserin aut Vajkoczy, Peter verfasserin aut Heppner, Frank L. verfasserin aut Capper, David verfasserin aut Hartmann, Wolfgang verfasserin aut Hartmann, Christian verfasserin aut von Deimling, Andreas verfasserin aut Reuss, David E. verfasserin aut Schöler, Anne verfasserin aut Koch, Arend verfasserin aut Enthalten in Acta neuropathologica Berlin : Springer, 1961 140(2020), 6 vom: 14. Sept., Seite 893-906 (DE-627)253389666 (DE-600)1458410-4 1432-0533 nnns volume:140 year:2020 number:6 day:14 month:09 pages:893-906 https://dx.doi.org/10.1007/s00401-020-02218-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 140 2020 6 14 09 893-906 |
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10.1007/s00401-020-02218-7 doi (DE-627)SPR041979060 (SPR)s00401-020-02218-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.90 bkl Schweizer, Leonille verfasserin aut Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Paraganglioma (dpeaa)DE-He213 Cauda equina (dpeaa)DE-He213 Head and neck (dpeaa)DE-He213 SDHB (dpeaa)DE-He213 GATA3 (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Thierfelder, Felix verfasserin aut Thomas, Christian verfasserin aut Soschinski, Patrick verfasserin aut Suwala, Abigail verfasserin aut Stichel, Damian verfasserin aut Wefers, Annika K. verfasserin aut Wessels, Lars verfasserin aut Misch, Martin verfasserin aut Kim, Hee-yeong verfasserin aut Jödicke, Ruben verfasserin aut Teichmann, Daniel verfasserin aut Kaul, David verfasserin aut Kahn, Johannes verfasserin aut Bockmayr, Michael verfasserin aut Hasselblatt, Martin verfasserin aut Younsi, Alexander verfasserin aut Unterberg, Andreas verfasserin aut Knie, Bettina verfasserin aut Walter, Jan verfasserin aut Al Safatli, Diaa verfasserin aut May, Sven-Axel verfasserin aut Jödicke, Andreas verfasserin aut Ntoulias, Georgios verfasserin aut Moskopp, Dag verfasserin aut Vajkoczy, Peter verfasserin aut Heppner, Frank L. verfasserin aut Capper, David verfasserin aut Hartmann, Wolfgang verfasserin aut Hartmann, Christian verfasserin aut von Deimling, Andreas verfasserin aut Reuss, David E. verfasserin aut Schöler, Anne verfasserin aut Koch, Arend verfasserin aut Enthalten in Acta neuropathologica Berlin : Springer, 1961 140(2020), 6 vom: 14. Sept., Seite 893-906 (DE-627)253389666 (DE-600)1458410-4 1432-0533 nnns volume:140 year:2020 number:6 day:14 month:09 pages:893-906 https://dx.doi.org/10.1007/s00401-020-02218-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 140 2020 6 14 09 893-906 |
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10.1007/s00401-020-02218-7 doi (DE-627)SPR041979060 (SPR)s00401-020-02218-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.90 bkl Schweizer, Leonille verfasserin aut Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Paraganglioma (dpeaa)DE-He213 Cauda equina (dpeaa)DE-He213 Head and neck (dpeaa)DE-He213 SDHB (dpeaa)DE-He213 GATA3 (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Thierfelder, Felix verfasserin aut Thomas, Christian verfasserin aut Soschinski, Patrick verfasserin aut Suwala, Abigail verfasserin aut Stichel, Damian verfasserin aut Wefers, Annika K. verfasserin aut Wessels, Lars verfasserin aut Misch, Martin verfasserin aut Kim, Hee-yeong verfasserin aut Jödicke, Ruben verfasserin aut Teichmann, Daniel verfasserin aut Kaul, David verfasserin aut Kahn, Johannes verfasserin aut Bockmayr, Michael verfasserin aut Hasselblatt, Martin verfasserin aut Younsi, Alexander verfasserin aut Unterberg, Andreas verfasserin aut Knie, Bettina verfasserin aut Walter, Jan verfasserin aut Al Safatli, Diaa verfasserin aut May, Sven-Axel verfasserin aut Jödicke, Andreas verfasserin aut Ntoulias, Georgios verfasserin aut Moskopp, Dag verfasserin aut Vajkoczy, Peter verfasserin aut Heppner, Frank L. verfasserin aut Capper, David verfasserin aut Hartmann, Wolfgang verfasserin aut Hartmann, Christian verfasserin aut von Deimling, Andreas verfasserin aut Reuss, David E. verfasserin aut Schöler, Anne verfasserin aut Koch, Arend verfasserin aut Enthalten in Acta neuropathologica Berlin : Springer, 1961 140(2020), 6 vom: 14. Sept., Seite 893-906 (DE-627)253389666 (DE-600)1458410-4 1432-0533 nnns volume:140 year:2020 number:6 day:14 month:09 pages:893-906 https://dx.doi.org/10.1007/s00401-020-02218-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 140 2020 6 14 09 893-906 |
| allfieldsSound |
10.1007/s00401-020-02218-7 doi (DE-627)SPR041979060 (SPR)s00401-020-02218-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.90 bkl Schweizer, Leonille verfasserin aut Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Paraganglioma (dpeaa)DE-He213 Cauda equina (dpeaa)DE-He213 Head and neck (dpeaa)DE-He213 SDHB (dpeaa)DE-He213 GATA3 (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Thierfelder, Felix verfasserin aut Thomas, Christian verfasserin aut Soschinski, Patrick verfasserin aut Suwala, Abigail verfasserin aut Stichel, Damian verfasserin aut Wefers, Annika K. verfasserin aut Wessels, Lars verfasserin aut Misch, Martin verfasserin aut Kim, Hee-yeong verfasserin aut Jödicke, Ruben verfasserin aut Teichmann, Daniel verfasserin aut Kaul, David verfasserin aut Kahn, Johannes verfasserin aut Bockmayr, Michael verfasserin aut Hasselblatt, Martin verfasserin aut Younsi, Alexander verfasserin aut Unterberg, Andreas verfasserin aut Knie, Bettina verfasserin aut Walter, Jan verfasserin aut Al Safatli, Diaa verfasserin aut May, Sven-Axel verfasserin aut Jödicke, Andreas verfasserin aut Ntoulias, Georgios verfasserin aut Moskopp, Dag verfasserin aut Vajkoczy, Peter verfasserin aut Heppner, Frank L. verfasserin aut Capper, David verfasserin aut Hartmann, Wolfgang verfasserin aut Hartmann, Christian verfasserin aut von Deimling, Andreas verfasserin aut Reuss, David E. verfasserin aut Schöler, Anne verfasserin aut Koch, Arend verfasserin aut Enthalten in Acta neuropathologica Berlin : Springer, 1961 140(2020), 6 vom: 14. Sept., Seite 893-906 (DE-627)253389666 (DE-600)1458410-4 1432-0533 nnns volume:140 year:2020 number:6 day:14 month:09 pages:893-906 https://dx.doi.org/10.1007/s00401-020-02218-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 140 2020 6 14 09 893-906 |
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Enthalten in Acta neuropathologica 140(2020), 6 vom: 14. Sept., Seite 893-906 volume:140 year:2020 number:6 day:14 month:09 pages:893-906 |
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Acta neuropathologica |
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Schweizer, Leonille @@aut@@ Thierfelder, Felix @@aut@@ Thomas, Christian @@aut@@ Soschinski, Patrick @@aut@@ Suwala, Abigail @@aut@@ Stichel, Damian @@aut@@ Wefers, Annika K. @@aut@@ Wessels, Lars @@aut@@ Misch, Martin @@aut@@ Kim, Hee-yeong @@aut@@ Jödicke, Ruben @@aut@@ Teichmann, Daniel @@aut@@ Kaul, David @@aut@@ Kahn, Johannes @@aut@@ Bockmayr, Michael @@aut@@ Hasselblatt, Martin @@aut@@ Younsi, Alexander @@aut@@ Unterberg, Andreas @@aut@@ Knie, Bettina @@aut@@ Walter, Jan @@aut@@ Al Safatli, Diaa @@aut@@ May, Sven-Axel @@aut@@ Jödicke, Andreas @@aut@@ Ntoulias, Georgios @@aut@@ Moskopp, Dag @@aut@@ Vajkoczy, Peter @@aut@@ Heppner, Frank L. @@aut@@ Capper, David @@aut@@ Hartmann, Wolfgang @@aut@@ Hartmann, Christian @@aut@@ von Deimling, Andreas @@aut@@ Reuss, David E. @@aut@@ Schöler, Anne @@aut@@ Koch, Arend @@aut@@ |
| publishDateDaySort_date |
2020-09-14T00:00:00Z |
| hierarchy_top_id |
253389666 |
| dewey-sort |
3610 |
| id |
SPR041979060 |
| language_de |
englisch |
| fullrecord |
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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. 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610 ASE 44.90 bkl Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity Paraganglioma (dpeaa)DE-He213 Cauda equina (dpeaa)DE-He213 Head and neck (dpeaa)DE-He213 SDHB (dpeaa)DE-He213 GATA3 (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 |
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Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity |
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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 |
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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 |
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Abstract 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. |
| abstractGer |
Abstract 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. |
| abstract_unstemmed |
Abstract 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. |
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