Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study
Abstract Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical dat...
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E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2019 |
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Enthalten in: Acta neuropathologica - Berlin : Springer, 1961, 139(2019), 2 vom: 09. Dez., Seite 223-241 |
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| Übergeordnetes Werk: |
volume:139 ; year:2019 ; number:2 ; day:09 ; month:12 ; pages:223-241 |
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| DOI / URN: |
10.1007/s00401-019-02111-y |
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| Katalog-ID: |
SPR004995279 |
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| 245 | 1 | 0 | |a Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study |
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| 520 | |a Abstract Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors. | ||
| 650 | 4 | |a Pineoblastoma |7 (dpeaa)DE-He213 | |
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| 650 | 4 | |a RB |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a MYC |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Vasiljevic, Alexandre |e verfasserin |4 aut | |
| 700 | 1 | |a Dufour, Christelle |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Fupan |e verfasserin |4 aut | |
| 700 | 1 | |a Ho, Ben L. B. |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Hwang, Eugene I. |e verfasserin |4 aut | |
| 700 | 1 | |a Gururangan, Sridharan |e verfasserin |4 aut | |
| 700 | 1 | |a Hansford, Jordan R. |e verfasserin |4 aut | |
| 700 | 1 | |a Fouladi, Maryam |e verfasserin |4 aut | |
| 700 | 1 | |a Nobusawa, Sumihito |e verfasserin |4 aut | |
| 700 | 1 | |a Laquerriere, Annie |e verfasserin |4 aut | |
| 700 | 1 | |a Delisle, Marie-Bernadette |e verfasserin |4 aut | |
| 700 | 1 | |a Fangusaro, Jason |e verfasserin |4 aut | |
| 700 | 1 | |a Forest, Fabien |e verfasserin |4 aut | |
| 700 | 1 | |a Toledano, Helen |e verfasserin |4 aut | |
| 700 | 1 | |a Solano-Paez, Palma |e verfasserin |4 aut | |
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| 700 | 1 | |a Birks, Diane |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffman, Lindsey M. |e verfasserin |4 aut | |
| 700 | 1 | |a Szathmari, Alexandru |e verfasserin |4 aut | |
| 700 | 1 | |a Faure-Conter, Cécile |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Catchpoole, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Schultz, Kris Ann P. |e verfasserin |4 aut | |
| 700 | 1 | |a Ichimura, Koichi |e verfasserin |4 aut | |
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| 700 | 1 | |a Pomeroy, Scott L. |e verfasserin |4 aut | |
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| 700 | 1 | |a Huang, Annie |e verfasserin |4 aut | |
| 700 | 1 | |a Jouvet, Anne |e verfasserin |4 aut | |
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10.1007/s00401-019-02111-y doi (DE-627)SPR004995279 (SPR)s00401-019-02111-y-e DE-627 ger DE-627 rakwb eng 610 ASE 44.90 bkl Li, Bryan K. verfasserin aut Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors. Pineoblastoma (dpeaa)DE-He213 PNET (dpeaa)DE-He213 PPTID (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 RB (dpeaa)DE-He213 MYC (dpeaa)DE-He213 Vasiljevic, Alexandre verfasserin aut Dufour, Christelle verfasserin aut Yao, Fupan verfasserin aut Ho, Ben L. B. verfasserin aut Lu, Mei verfasserin aut Hwang, Eugene I. verfasserin aut Gururangan, Sridharan verfasserin aut Hansford, Jordan R. verfasserin aut Fouladi, Maryam verfasserin aut Nobusawa, Sumihito verfasserin aut Laquerriere, Annie verfasserin aut Delisle, Marie-Bernadette verfasserin aut Fangusaro, Jason verfasserin aut Forest, Fabien verfasserin aut Toledano, Helen verfasserin aut Solano-Paez, Palma verfasserin aut Leary, Sarah verfasserin aut Birks, Diane verfasserin aut Hoffman, Lindsey M. verfasserin aut Szathmari, Alexandru verfasserin aut Faure-Conter, Cécile verfasserin aut Fan, Xing verfasserin aut Catchpoole, Daniel verfasserin aut Zhou, Li verfasserin aut Schultz, Kris Ann P. verfasserin aut Ichimura, Koichi verfasserin aut Gauchotte, Guillaume verfasserin aut Jabado, Nada verfasserin aut Jones, Chris verfasserin aut Loussouarn, Delphine verfasserin aut Mokhtari, Karima verfasserin aut Rousseau, Audrey verfasserin aut Ziegler, David S. verfasserin aut Tanaka, Shinya verfasserin aut Pomeroy, Scott L. verfasserin aut Gajjar, Amar verfasserin aut Ramaswamy, Vijay verfasserin aut Hawkins, Cynthia verfasserin aut Grundy, Richard G. verfasserin aut Hill, D. Ashley verfasserin aut Bouffet, Eric verfasserin aut Huang, Annie verfasserin aut Jouvet, Anne verfasserin aut Enthalten in Acta neuropathologica Berlin : Springer, 1961 139(2019), 2 vom: 09. Dez., Seite 223-241 (DE-627)253389666 (DE-600)1458410-4 1432-0533 nnns volume:139 year:2019 number:2 day:09 month:12 pages:223-241 https://dx.doi.org/10.1007/s00401-019-02111-y lizenzpflichtig 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_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 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_2116 GBV_ILN_2118 GBV_ILN_2119 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_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 139 2019 2 09 12 223-241 |
| spelling |
10.1007/s00401-019-02111-y doi (DE-627)SPR004995279 (SPR)s00401-019-02111-y-e DE-627 ger DE-627 rakwb eng 610 ASE 44.90 bkl Li, Bryan K. verfasserin aut Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors. Pineoblastoma (dpeaa)DE-He213 PNET (dpeaa)DE-He213 PPTID (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 RB (dpeaa)DE-He213 MYC (dpeaa)DE-He213 Vasiljevic, Alexandre verfasserin aut Dufour, Christelle verfasserin aut Yao, Fupan verfasserin aut Ho, Ben L. B. verfasserin aut Lu, Mei verfasserin aut Hwang, Eugene I. verfasserin aut Gururangan, Sridharan verfasserin aut Hansford, Jordan R. verfasserin aut Fouladi, Maryam verfasserin aut Nobusawa, Sumihito verfasserin aut Laquerriere, Annie verfasserin aut Delisle, Marie-Bernadette verfasserin aut Fangusaro, Jason verfasserin aut Forest, Fabien verfasserin aut Toledano, Helen verfasserin aut Solano-Paez, Palma verfasserin aut Leary, Sarah verfasserin aut Birks, Diane verfasserin aut Hoffman, Lindsey M. verfasserin aut Szathmari, Alexandru verfasserin aut Faure-Conter, Cécile verfasserin aut Fan, Xing verfasserin aut Catchpoole, Daniel verfasserin aut Zhou, Li verfasserin aut Schultz, Kris Ann P. verfasserin aut Ichimura, Koichi verfasserin aut Gauchotte, Guillaume verfasserin aut Jabado, Nada verfasserin aut Jones, Chris verfasserin aut Loussouarn, Delphine verfasserin aut Mokhtari, Karima verfasserin aut Rousseau, Audrey verfasserin aut Ziegler, David S. verfasserin aut Tanaka, Shinya verfasserin aut Pomeroy, Scott L. verfasserin aut Gajjar, Amar verfasserin aut Ramaswamy, Vijay verfasserin aut Hawkins, Cynthia verfasserin aut Grundy, Richard G. verfasserin aut Hill, D. Ashley verfasserin aut Bouffet, Eric verfasserin aut Huang, Annie verfasserin aut Jouvet, Anne verfasserin aut Enthalten in Acta neuropathologica Berlin : Springer, 1961 139(2019), 2 vom: 09. Dez., Seite 223-241 (DE-627)253389666 (DE-600)1458410-4 1432-0533 nnns volume:139 year:2019 number:2 day:09 month:12 pages:223-241 https://dx.doi.org/10.1007/s00401-019-02111-y lizenzpflichtig 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_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 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_2116 GBV_ILN_2118 GBV_ILN_2119 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_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 139 2019 2 09 12 223-241 |
| allfields_unstemmed |
10.1007/s00401-019-02111-y doi (DE-627)SPR004995279 (SPR)s00401-019-02111-y-e DE-627 ger DE-627 rakwb eng 610 ASE 44.90 bkl Li, Bryan K. verfasserin aut Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors. Pineoblastoma (dpeaa)DE-He213 PNET (dpeaa)DE-He213 PPTID (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 RB (dpeaa)DE-He213 MYC (dpeaa)DE-He213 Vasiljevic, Alexandre verfasserin aut Dufour, Christelle verfasserin aut Yao, Fupan verfasserin aut Ho, Ben L. B. verfasserin aut Lu, Mei verfasserin aut Hwang, Eugene I. verfasserin aut Gururangan, Sridharan verfasserin aut Hansford, Jordan R. verfasserin aut Fouladi, Maryam verfasserin aut Nobusawa, Sumihito verfasserin aut Laquerriere, Annie verfasserin aut Delisle, Marie-Bernadette verfasserin aut Fangusaro, Jason verfasserin aut Forest, Fabien verfasserin aut Toledano, Helen verfasserin aut Solano-Paez, Palma verfasserin aut Leary, Sarah verfasserin aut Birks, Diane verfasserin aut Hoffman, Lindsey M. verfasserin aut Szathmari, Alexandru verfasserin aut Faure-Conter, Cécile verfasserin aut Fan, Xing verfasserin aut Catchpoole, Daniel verfasserin aut Zhou, Li verfasserin aut Schultz, Kris Ann P. verfasserin aut Ichimura, Koichi verfasserin aut Gauchotte, Guillaume verfasserin aut Jabado, Nada verfasserin aut Jones, Chris verfasserin aut Loussouarn, Delphine verfasserin aut Mokhtari, Karima verfasserin aut Rousseau, Audrey verfasserin aut Ziegler, David S. verfasserin aut Tanaka, Shinya verfasserin aut Pomeroy, Scott L. verfasserin aut Gajjar, Amar verfasserin aut Ramaswamy, Vijay verfasserin aut Hawkins, Cynthia verfasserin aut Grundy, Richard G. verfasserin aut Hill, D. Ashley verfasserin aut Bouffet, Eric verfasserin aut Huang, Annie verfasserin aut Jouvet, Anne verfasserin aut Enthalten in Acta neuropathologica Berlin : Springer, 1961 139(2019), 2 vom: 09. Dez., Seite 223-241 (DE-627)253389666 (DE-600)1458410-4 1432-0533 nnns volume:139 year:2019 number:2 day:09 month:12 pages:223-241 https://dx.doi.org/10.1007/s00401-019-02111-y lizenzpflichtig 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_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 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_2116 GBV_ILN_2118 GBV_ILN_2119 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_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 139 2019 2 09 12 223-241 |
| allfieldsGer |
10.1007/s00401-019-02111-y doi (DE-627)SPR004995279 (SPR)s00401-019-02111-y-e DE-627 ger DE-627 rakwb eng 610 ASE 44.90 bkl Li, Bryan K. verfasserin aut Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors. Pineoblastoma (dpeaa)DE-He213 PNET (dpeaa)DE-He213 PPTID (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 RB (dpeaa)DE-He213 MYC (dpeaa)DE-He213 Vasiljevic, Alexandre verfasserin aut Dufour, Christelle verfasserin aut Yao, Fupan verfasserin aut Ho, Ben L. B. verfasserin aut Lu, Mei verfasserin aut Hwang, Eugene I. verfasserin aut Gururangan, Sridharan verfasserin aut Hansford, Jordan R. verfasserin aut Fouladi, Maryam verfasserin aut Nobusawa, Sumihito verfasserin aut Laquerriere, Annie verfasserin aut Delisle, Marie-Bernadette verfasserin aut Fangusaro, Jason verfasserin aut Forest, Fabien verfasserin aut Toledano, Helen verfasserin aut Solano-Paez, Palma verfasserin aut Leary, Sarah verfasserin aut Birks, Diane verfasserin aut Hoffman, Lindsey M. verfasserin aut Szathmari, Alexandru verfasserin aut Faure-Conter, Cécile verfasserin aut Fan, Xing verfasserin aut Catchpoole, Daniel verfasserin aut Zhou, Li verfasserin aut Schultz, Kris Ann P. verfasserin aut Ichimura, Koichi verfasserin aut Gauchotte, Guillaume verfasserin aut Jabado, Nada verfasserin aut Jones, Chris verfasserin aut Loussouarn, Delphine verfasserin aut Mokhtari, Karima verfasserin aut Rousseau, Audrey verfasserin aut Ziegler, David S. verfasserin aut Tanaka, Shinya verfasserin aut Pomeroy, Scott L. verfasserin aut Gajjar, Amar verfasserin aut Ramaswamy, Vijay verfasserin aut Hawkins, Cynthia verfasserin aut Grundy, Richard G. verfasserin aut Hill, D. Ashley verfasserin aut Bouffet, Eric verfasserin aut Huang, Annie verfasserin aut Jouvet, Anne verfasserin aut Enthalten in Acta neuropathologica Berlin : Springer, 1961 139(2019), 2 vom: 09. Dez., Seite 223-241 (DE-627)253389666 (DE-600)1458410-4 1432-0533 nnns volume:139 year:2019 number:2 day:09 month:12 pages:223-241 https://dx.doi.org/10.1007/s00401-019-02111-y lizenzpflichtig 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_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 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_2116 GBV_ILN_2118 GBV_ILN_2119 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_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 139 2019 2 09 12 223-241 |
| allfieldsSound |
10.1007/s00401-019-02111-y doi (DE-627)SPR004995279 (SPR)s00401-019-02111-y-e DE-627 ger DE-627 rakwb eng 610 ASE 44.90 bkl Li, Bryan K. verfasserin aut Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors. Pineoblastoma (dpeaa)DE-He213 PNET (dpeaa)DE-He213 PPTID (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 RB (dpeaa)DE-He213 MYC (dpeaa)DE-He213 Vasiljevic, Alexandre verfasserin aut Dufour, Christelle verfasserin aut Yao, Fupan verfasserin aut Ho, Ben L. B. verfasserin aut Lu, Mei verfasserin aut Hwang, Eugene I. verfasserin aut Gururangan, Sridharan verfasserin aut Hansford, Jordan R. verfasserin aut Fouladi, Maryam verfasserin aut Nobusawa, Sumihito verfasserin aut Laquerriere, Annie verfasserin aut Delisle, Marie-Bernadette verfasserin aut Fangusaro, Jason verfasserin aut Forest, Fabien verfasserin aut Toledano, Helen verfasserin aut Solano-Paez, Palma verfasserin aut Leary, Sarah verfasserin aut Birks, Diane verfasserin aut Hoffman, Lindsey M. verfasserin aut Szathmari, Alexandru verfasserin aut Faure-Conter, Cécile verfasserin aut Fan, Xing verfasserin aut Catchpoole, Daniel verfasserin aut Zhou, Li verfasserin aut Schultz, Kris Ann P. verfasserin aut Ichimura, Koichi verfasserin aut Gauchotte, Guillaume verfasserin aut Jabado, Nada verfasserin aut Jones, Chris verfasserin aut Loussouarn, Delphine verfasserin aut Mokhtari, Karima verfasserin aut Rousseau, Audrey verfasserin aut Ziegler, David S. verfasserin aut Tanaka, Shinya verfasserin aut Pomeroy, Scott L. verfasserin aut Gajjar, Amar verfasserin aut Ramaswamy, Vijay verfasserin aut Hawkins, Cynthia verfasserin aut Grundy, Richard G. verfasserin aut Hill, D. Ashley verfasserin aut Bouffet, Eric verfasserin aut Huang, Annie verfasserin aut Jouvet, Anne verfasserin aut Enthalten in Acta neuropathologica Berlin : Springer, 1961 139(2019), 2 vom: 09. Dez., Seite 223-241 (DE-627)253389666 (DE-600)1458410-4 1432-0533 nnns volume:139 year:2019 number:2 day:09 month:12 pages:223-241 https://dx.doi.org/10.1007/s00401-019-02111-y lizenzpflichtig 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_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 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_2116 GBV_ILN_2118 GBV_ILN_2119 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_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 139 2019 2 09 12 223-241 |
| language |
English |
| source |
Enthalten in Acta neuropathologica 139(2019), 2 vom: 09. Dez., Seite 223-241 volume:139 year:2019 number:2 day:09 month:12 pages:223-241 |
| sourceStr |
Enthalten in Acta neuropathologica 139(2019), 2 vom: 09. Dez., Seite 223-241 volume:139 year:2019 number:2 day:09 month:12 pages:223-241 |
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Article |
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findex.gbv.de |
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Pineoblastoma PNET PPTID miRNA RB MYC |
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Acta neuropathologica |
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Li, Bryan K. @@aut@@ Vasiljevic, Alexandre @@aut@@ Dufour, Christelle @@aut@@ Yao, Fupan @@aut@@ Ho, Ben L. B. @@aut@@ Lu, Mei @@aut@@ Hwang, Eugene I. @@aut@@ Gururangan, Sridharan @@aut@@ Hansford, Jordan R. @@aut@@ Fouladi, Maryam @@aut@@ Nobusawa, Sumihito @@aut@@ Laquerriere, Annie @@aut@@ Delisle, Marie-Bernadette @@aut@@ Fangusaro, Jason @@aut@@ Forest, Fabien @@aut@@ Toledano, Helen @@aut@@ Solano-Paez, Palma @@aut@@ Leary, Sarah @@aut@@ Birks, Diane @@aut@@ Hoffman, Lindsey M. @@aut@@ Szathmari, Alexandru @@aut@@ Faure-Conter, Cécile @@aut@@ Fan, Xing @@aut@@ Catchpoole, Daniel @@aut@@ Zhou, Li @@aut@@ Schultz, Kris Ann P. @@aut@@ Ichimura, Koichi @@aut@@ Gauchotte, Guillaume @@aut@@ Jabado, Nada @@aut@@ Jones, Chris @@aut@@ Loussouarn, Delphine @@aut@@ Mokhtari, Karima @@aut@@ Rousseau, Audrey @@aut@@ Ziegler, David S. @@aut@@ Tanaka, Shinya @@aut@@ Pomeroy, Scott L. @@aut@@ Gajjar, Amar @@aut@@ Ramaswamy, Vijay @@aut@@ Hawkins, Cynthia @@aut@@ Grundy, Richard G. @@aut@@ Hill, D. Ashley @@aut@@ Bouffet, Eric @@aut@@ Huang, Annie @@aut@@ Jouvet, Anne @@aut@@ |
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2019-12-09T00:00:00Z |
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3610 |
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SPR004995279 |
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englisch |
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| author |
Li, Bryan K. |
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Li, Bryan K. ddc 610 bkl 44.90 misc Pineoblastoma misc PNET misc PPTID misc miRNA misc RB misc MYC Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study |
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610 ASE 44.90 bkl Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study Pineoblastoma (dpeaa)DE-He213 PNET (dpeaa)DE-He213 PPTID (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 RB (dpeaa)DE-He213 MYC (dpeaa)DE-He213 |
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ddc 610 bkl 44.90 misc Pineoblastoma misc PNET misc PPTID misc miRNA misc RB misc MYC |
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ddc 610 bkl 44.90 misc Pineoblastoma misc PNET misc PPTID misc miRNA misc RB misc MYC |
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ddc 610 bkl 44.90 misc Pineoblastoma misc PNET misc PPTID misc miRNA misc RB misc MYC |
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Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study |
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Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study |
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Li, Bryan K. |
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Acta neuropathologica |
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Li, Bryan K. Vasiljevic, Alexandre Dufour, Christelle Yao, Fupan Ho, Ben L. B. Lu, Mei Hwang, Eugene I. Gururangan, Sridharan Hansford, Jordan R. Fouladi, Maryam Nobusawa, Sumihito Laquerriere, Annie Delisle, Marie-Bernadette Fangusaro, Jason Forest, Fabien Toledano, Helen Solano-Paez, Palma Leary, Sarah Birks, Diane Hoffman, Lindsey M. Szathmari, Alexandru Faure-Conter, Cécile Fan, Xing Catchpoole, Daniel Zhou, Li Schultz, Kris Ann P. Ichimura, Koichi Gauchotte, Guillaume Jabado, Nada Jones, Chris Loussouarn, Delphine Mokhtari, Karima Rousseau, Audrey Ziegler, David S. Tanaka, Shinya Pomeroy, Scott L. Gajjar, Amar Ramaswamy, Vijay Hawkins, Cynthia Grundy, Richard G. Hill, D. Ashley Bouffet, Eric Huang, Annie Jouvet, Anne |
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Li, Bryan K. |
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pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a rare brain tumor consortium registry study |
| title_auth |
Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study |
| abstract |
Abstract Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors. |
| abstractGer |
Abstract Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors. |
| abstract_unstemmed |
Abstract Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors. |
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Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study |
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https://dx.doi.org/10.1007/s00401-019-02111-y |
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Vasiljevic, Alexandre Dufour, Christelle Yao, Fupan Ho, Ben L. B. Lu, Mei Hwang, Eugene I. Gururangan, Sridharan Hansford, Jordan R. Fouladi, Maryam Nobusawa, Sumihito Laquerriere, Annie Delisle, Marie-Bernadette Fangusaro, Jason Forest, Fabien Toledano, Helen Solano-Paez, Palma Leary, Sarah Birks, Diane Hoffman, Lindsey M. Szathmari, Alexandru Faure-Conter, Cécile Fan, Xing Catchpoole, Daniel Zhou, Li Schultz, Kris Ann P. Ichimura, Koichi Gauchotte, Guillaume Jabado, Nada Jones, Chris Loussouarn, Delphine Mokhtari, Karima Rousseau, Audrey Ziegler, David S. Tanaka, Shinya Pomeroy, Scott L. Gajjar, Amar Ramaswamy, Vijay Hawkins, Cynthia Grundy, Richard G. Hill, D. Ashley Bouffet, Eric Huang, Annie Jouvet, Anne |
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Vasiljevic, Alexandre Dufour, Christelle Yao, Fupan Ho, Ben L. B. Lu, Mei Hwang, Eugene I. Gururangan, Sridharan Hansford, Jordan R. Fouladi, Maryam Nobusawa, Sumihito Laquerriere, Annie Delisle, Marie-Bernadette Fangusaro, Jason Forest, Fabien Toledano, Helen Solano-Paez, Palma Leary, Sarah Birks, Diane Hoffman, Lindsey M. Szathmari, Alexandru Faure-Conter, Cécile Fan, Xing Catchpoole, Daniel Zhou, Li Schultz, Kris Ann P. Ichimura, Koichi Gauchotte, Guillaume Jabado, Nada Jones, Chris Loussouarn, Delphine Mokhtari, Karima Rousseau, Audrey Ziegler, David S. Tanaka, Shinya Pomeroy, Scott L. Gajjar, Amar Ramaswamy, Vijay Hawkins, Cynthia Grundy, Richard G. Hill, D. Ashley Bouffet, Eric Huang, Annie Jouvet, Anne |
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10.1007/s00401-019-02111-y |
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2024-07-04T03:20:24.637Z |
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| score |
7.401101 |