A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide

Background Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic...
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Autor*in:	Chatzikyriakou, Prodromos [verfasserIn] Brempou, Dimitria Quinn, Mark Fishbein, Lauren Noberini, Roberta Anastopoulos, Ioannis N. Tufton, Nicola Lim, Eugenie S. Obholzer, Rupert Hubbard, Johnathan G. Moonim, Mufaddal Bonaldi, Tiziana Nathanson, Katherine L. Izatt, Louise Oakey, Rebecca J.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Phaeochromocytoma Paraganglioma DNA methylation Epigenetics Succinate dehydrogenase Histone post-translational modifications Mass spectrometry SDH Cancer predisposition Germline pathogenic variant

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: Clinical epigenetics - [S.l.] : BioMed Central, 2010, 15(2023), 1 vom: 20. Dez.
Übergeordnetes Werk:	volume:15 ; year:2023 ; number:1 ; day:20 ; month:12

Links:	Volltext

DOI / URN:	10.1186/s13148-023-01598-3

Katalog-ID:	SPR054147778

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520			\|a Background Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic variants affecting enzymes of the tricarboxylic acid cycle, including succinate dehydrogenase. Within inherited PPGLs, these are the most common. PPGL tumours are known to undergo epigenetic reprograming, and here, we report on global histone post-translational modifications and DNA methylation levels, alongside clinical phenotypes. Results Out of the 25 histone post-translational modifications examined, Cluster 1A PPGLs were distinguished from other tumours by a decrease in hyper-acetylated peptides and an increase in H3K4me2. DNA methylation was compared between tumours from individuals who developed metastatic disease versus those that did not. The majority of differentially methylated sites identified tended to be completely methylated or unmethylated in non-metastatic tumours, with low inter-sample variance. Metastatic tumours by contrast consistently had an intermediate DNA methylation state, including the ephrin receptor EPHA4 and its ligand EFNA3. Gene expression analyses performed to identify genes involved in metastatic tumour behaviour pin-pointed a number of genes previously described as mis-regulated in Cluster 1A tumours, as well as highlighting the tumour suppressor RGS22 and the pituitary tumour-transforming gene PTTG1. Conclusions Combined transcriptomic and DNA methylation analyses revealed aberrant pathways, including ones that could be implicated in metastatic phenotypes and, for the first time, we report a decrease in hyper-acetylated histone marks in Cluster 1 PPGLs.
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allfields	10.1186/s13148-023-01598-3 doi (DE-627)SPR054147778 (SPR)s13148-023-01598-3-e DE-627 ger DE-627 rakwb eng Chatzikyriakou, Prodromos verfasserin aut A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic variants affecting enzymes of the tricarboxylic acid cycle, including succinate dehydrogenase. Within inherited PPGLs, these are the most common. PPGL tumours are known to undergo epigenetic reprograming, and here, we report on global histone post-translational modifications and DNA methylation levels, alongside clinical phenotypes. Results Out of the 25 histone post-translational modifications examined, Cluster 1A PPGLs were distinguished from other tumours by a decrease in hyper-acetylated peptides and an increase in H3K4me2. DNA methylation was compared between tumours from individuals who developed metastatic disease versus those that did not. The majority of differentially methylated sites identified tended to be completely methylated or unmethylated in non-metastatic tumours, with low inter-sample variance. Metastatic tumours by contrast consistently had an intermediate DNA methylation state, including the ephrin receptor EPHA4 and its ligand EFNA3. Gene expression analyses performed to identify genes involved in metastatic tumour behaviour pin-pointed a number of genes previously described as mis-regulated in Cluster 1A tumours, as well as highlighting the tumour suppressor RGS22 and the pituitary tumour-transforming gene PTTG1. Conclusions Combined transcriptomic and DNA methylation analyses revealed aberrant pathways, including ones that could be implicated in metastatic phenotypes and, for the first time, we report a decrease in hyper-acetylated histone marks in Cluster 1 PPGLs. Phaeochromocytoma (dpeaa)DE-He213 Paraganglioma (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Succinate dehydrogenase (dpeaa)DE-He213 Histone post-translational modifications (dpeaa)DE-He213 Mass spectrometry (dpeaa)DE-He213 SDH (dpeaa)DE-He213 Cancer predisposition (dpeaa)DE-He213 Germline pathogenic variant (dpeaa)DE-He213 Brempou, Dimitria aut Quinn, Mark aut Fishbein, Lauren aut Noberini, Roberta aut Anastopoulos, Ioannis N. aut Tufton, Nicola aut Lim, Eugenie S. aut Obholzer, Rupert aut Hubbard, Johnathan G. aut Moonim, Mufaddal aut Bonaldi, Tiziana aut Nathanson, Katherine L. aut Izatt, Louise aut Oakey, Rebecca J. aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 15(2023), 1 vom: 20. Dez. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:15 year:2023 number:1 day:20 month:12 https://dx.doi.org/10.1186/s13148-023-01598-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 20 12
spelling	10.1186/s13148-023-01598-3 doi (DE-627)SPR054147778 (SPR)s13148-023-01598-3-e DE-627 ger DE-627 rakwb eng Chatzikyriakou, Prodromos verfasserin aut A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic variants affecting enzymes of the tricarboxylic acid cycle, including succinate dehydrogenase. Within inherited PPGLs, these are the most common. PPGL tumours are known to undergo epigenetic reprograming, and here, we report on global histone post-translational modifications and DNA methylation levels, alongside clinical phenotypes. Results Out of the 25 histone post-translational modifications examined, Cluster 1A PPGLs were distinguished from other tumours by a decrease in hyper-acetylated peptides and an increase in H3K4me2. DNA methylation was compared between tumours from individuals who developed metastatic disease versus those that did not. The majority of differentially methylated sites identified tended to be completely methylated or unmethylated in non-metastatic tumours, with low inter-sample variance. Metastatic tumours by contrast consistently had an intermediate DNA methylation state, including the ephrin receptor EPHA4 and its ligand EFNA3. Gene expression analyses performed to identify genes involved in metastatic tumour behaviour pin-pointed a number of genes previously described as mis-regulated in Cluster 1A tumours, as well as highlighting the tumour suppressor RGS22 and the pituitary tumour-transforming gene PTTG1. Conclusions Combined transcriptomic and DNA methylation analyses revealed aberrant pathways, including ones that could be implicated in metastatic phenotypes and, for the first time, we report a decrease in hyper-acetylated histone marks in Cluster 1 PPGLs. Phaeochromocytoma (dpeaa)DE-He213 Paraganglioma (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Succinate dehydrogenase (dpeaa)DE-He213 Histone post-translational modifications (dpeaa)DE-He213 Mass spectrometry (dpeaa)DE-He213 SDH (dpeaa)DE-He213 Cancer predisposition (dpeaa)DE-He213 Germline pathogenic variant (dpeaa)DE-He213 Brempou, Dimitria aut Quinn, Mark aut Fishbein, Lauren aut Noberini, Roberta aut Anastopoulos, Ioannis N. aut Tufton, Nicola aut Lim, Eugenie S. aut Obholzer, Rupert aut Hubbard, Johnathan G. aut Moonim, Mufaddal aut Bonaldi, Tiziana aut Nathanson, Katherine L. aut Izatt, Louise aut Oakey, Rebecca J. aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 15(2023), 1 vom: 20. Dez. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:15 year:2023 number:1 day:20 month:12 https://dx.doi.org/10.1186/s13148-023-01598-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 20 12
allfields_unstemmed	10.1186/s13148-023-01598-3 doi (DE-627)SPR054147778 (SPR)s13148-023-01598-3-e DE-627 ger DE-627 rakwb eng Chatzikyriakou, Prodromos verfasserin aut A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic variants affecting enzymes of the tricarboxylic acid cycle, including succinate dehydrogenase. Within inherited PPGLs, these are the most common. PPGL tumours are known to undergo epigenetic reprograming, and here, we report on global histone post-translational modifications and DNA methylation levels, alongside clinical phenotypes. Results Out of the 25 histone post-translational modifications examined, Cluster 1A PPGLs were distinguished from other tumours by a decrease in hyper-acetylated peptides and an increase in H3K4me2. DNA methylation was compared between tumours from individuals who developed metastatic disease versus those that did not. The majority of differentially methylated sites identified tended to be completely methylated or unmethylated in non-metastatic tumours, with low inter-sample variance. Metastatic tumours by contrast consistently had an intermediate DNA methylation state, including the ephrin receptor EPHA4 and its ligand EFNA3. Gene expression analyses performed to identify genes involved in metastatic tumour behaviour pin-pointed a number of genes previously described as mis-regulated in Cluster 1A tumours, as well as highlighting the tumour suppressor RGS22 and the pituitary tumour-transforming gene PTTG1. Conclusions Combined transcriptomic and DNA methylation analyses revealed aberrant pathways, including ones that could be implicated in metastatic phenotypes and, for the first time, we report a decrease in hyper-acetylated histone marks in Cluster 1 PPGLs. Phaeochromocytoma (dpeaa)DE-He213 Paraganglioma (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Succinate dehydrogenase (dpeaa)DE-He213 Histone post-translational modifications (dpeaa)DE-He213 Mass spectrometry (dpeaa)DE-He213 SDH (dpeaa)DE-He213 Cancer predisposition (dpeaa)DE-He213 Germline pathogenic variant (dpeaa)DE-He213 Brempou, Dimitria aut Quinn, Mark aut Fishbein, Lauren aut Noberini, Roberta aut Anastopoulos, Ioannis N. aut Tufton, Nicola aut Lim, Eugenie S. aut Obholzer, Rupert aut Hubbard, Johnathan G. aut Moonim, Mufaddal aut Bonaldi, Tiziana aut Nathanson, Katherine L. aut Izatt, Louise aut Oakey, Rebecca J. aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 15(2023), 1 vom: 20. Dez. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:15 year:2023 number:1 day:20 month:12 https://dx.doi.org/10.1186/s13148-023-01598-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 20 12
allfieldsGer	10.1186/s13148-023-01598-3 doi (DE-627)SPR054147778 (SPR)s13148-023-01598-3-e DE-627 ger DE-627 rakwb eng Chatzikyriakou, Prodromos verfasserin aut A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic variants affecting enzymes of the tricarboxylic acid cycle, including succinate dehydrogenase. Within inherited PPGLs, these are the most common. PPGL tumours are known to undergo epigenetic reprograming, and here, we report on global histone post-translational modifications and DNA methylation levels, alongside clinical phenotypes. Results Out of the 25 histone post-translational modifications examined, Cluster 1A PPGLs were distinguished from other tumours by a decrease in hyper-acetylated peptides and an increase in H3K4me2. DNA methylation was compared between tumours from individuals who developed metastatic disease versus those that did not. The majority of differentially methylated sites identified tended to be completely methylated or unmethylated in non-metastatic tumours, with low inter-sample variance. Metastatic tumours by contrast consistently had an intermediate DNA methylation state, including the ephrin receptor EPHA4 and its ligand EFNA3. Gene expression analyses performed to identify genes involved in metastatic tumour behaviour pin-pointed a number of genes previously described as mis-regulated in Cluster 1A tumours, as well as highlighting the tumour suppressor RGS22 and the pituitary tumour-transforming gene PTTG1. Conclusions Combined transcriptomic and DNA methylation analyses revealed aberrant pathways, including ones that could be implicated in metastatic phenotypes and, for the first time, we report a decrease in hyper-acetylated histone marks in Cluster 1 PPGLs. Phaeochromocytoma (dpeaa)DE-He213 Paraganglioma (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Succinate dehydrogenase (dpeaa)DE-He213 Histone post-translational modifications (dpeaa)DE-He213 Mass spectrometry (dpeaa)DE-He213 SDH (dpeaa)DE-He213 Cancer predisposition (dpeaa)DE-He213 Germline pathogenic variant (dpeaa)DE-He213 Brempou, Dimitria aut Quinn, Mark aut Fishbein, Lauren aut Noberini, Roberta aut Anastopoulos, Ioannis N. aut Tufton, Nicola aut Lim, Eugenie S. aut Obholzer, Rupert aut Hubbard, Johnathan G. aut Moonim, Mufaddal aut Bonaldi, Tiziana aut Nathanson, Katherine L. aut Izatt, Louise aut Oakey, Rebecca J. aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 15(2023), 1 vom: 20. Dez. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:15 year:2023 number:1 day:20 month:12 https://dx.doi.org/10.1186/s13148-023-01598-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 20 12
allfieldsSound	10.1186/s13148-023-01598-3 doi (DE-627)SPR054147778 (SPR)s13148-023-01598-3-e DE-627 ger DE-627 rakwb eng Chatzikyriakou, Prodromos verfasserin aut A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic variants affecting enzymes of the tricarboxylic acid cycle, including succinate dehydrogenase. Within inherited PPGLs, these are the most common. PPGL tumours are known to undergo epigenetic reprograming, and here, we report on global histone post-translational modifications and DNA methylation levels, alongside clinical phenotypes. Results Out of the 25 histone post-translational modifications examined, Cluster 1A PPGLs were distinguished from other tumours by a decrease in hyper-acetylated peptides and an increase in H3K4me2. DNA methylation was compared between tumours from individuals who developed metastatic disease versus those that did not. The majority of differentially methylated sites identified tended to be completely methylated or unmethylated in non-metastatic tumours, with low inter-sample variance. Metastatic tumours by contrast consistently had an intermediate DNA methylation state, including the ephrin receptor EPHA4 and its ligand EFNA3. Gene expression analyses performed to identify genes involved in metastatic tumour behaviour pin-pointed a number of genes previously described as mis-regulated in Cluster 1A tumours, as well as highlighting the tumour suppressor RGS22 and the pituitary tumour-transforming gene PTTG1. Conclusions Combined transcriptomic and DNA methylation analyses revealed aberrant pathways, including ones that could be implicated in metastatic phenotypes and, for the first time, we report a decrease in hyper-acetylated histone marks in Cluster 1 PPGLs. Phaeochromocytoma (dpeaa)DE-He213 Paraganglioma (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Succinate dehydrogenase (dpeaa)DE-He213 Histone post-translational modifications (dpeaa)DE-He213 Mass spectrometry (dpeaa)DE-He213 SDH (dpeaa)DE-He213 Cancer predisposition (dpeaa)DE-He213 Germline pathogenic variant (dpeaa)DE-He213 Brempou, Dimitria aut Quinn, Mark aut Fishbein, Lauren aut Noberini, Roberta aut Anastopoulos, Ioannis N. aut Tufton, Nicola aut Lim, Eugenie S. aut Obholzer, Rupert aut Hubbard, Johnathan G. aut Moonim, Mufaddal aut Bonaldi, Tiziana aut Nathanson, Katherine L. aut Izatt, Louise aut Oakey, Rebecca J. aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 15(2023), 1 vom: 20. Dez. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:15 year:2023 number:1 day:20 month:12 https://dx.doi.org/10.1186/s13148-023-01598-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 20 12
language	English
source	Enthalten in Clinical epigenetics 15(2023), 1 vom: 20. Dez. volume:15 year:2023 number:1 day:20 month:12
sourceStr	Enthalten in Clinical epigenetics 15(2023), 1 vom: 20. Dez. volume:15 year:2023 number:1 day:20 month:12
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Phaeochromocytoma Paraganglioma DNA methylation Epigenetics Succinate dehydrogenase Histone post-translational modifications Mass spectrometry SDH Cancer predisposition Germline pathogenic variant
isfreeaccess_bool	true
container_title	Clinical epigenetics
authorswithroles_txt_mv	Chatzikyriakou, Prodromos @@aut@@ Brempou, Dimitria @@aut@@ Quinn, Mark @@aut@@ Fishbein, Lauren @@aut@@ Noberini, Roberta @@aut@@ Anastopoulos, Ioannis N. @@aut@@ Tufton, Nicola @@aut@@ Lim, Eugenie S. @@aut@@ Obholzer, Rupert @@aut@@ Hubbard, Johnathan G. @@aut@@ Moonim, Mufaddal @@aut@@ Bonaldi, Tiziana @@aut@@ Nathanson, Katherine L. @@aut@@ Izatt, Louise @@aut@@ Oakey, Rebecca J. @@aut@@
publishDateDaySort_date	2023-12-20T00:00:00Z
hierarchy_top_id	626459028
id	SPR054147778
language_de	englisch
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The majority of differentially methylated sites identified tended to be completely methylated or unmethylated in non-metastatic tumours, with low inter-sample variance. Metastatic tumours by contrast consistently had an intermediate DNA methylation state, including the ephrin receptor EPHA4 and its ligand EFNA3. Gene expression analyses performed to identify genes involved in metastatic tumour behaviour pin-pointed a number of genes previously described as mis-regulated in Cluster 1A tumours, as well as highlighting the tumour suppressor RGS22 and the pituitary tumour-transforming gene PTTG1. 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author	Chatzikyriakou, Prodromos
spellingShingle	Chatzikyriakou, Prodromos misc Phaeochromocytoma misc Paraganglioma misc DNA methylation misc Epigenetics misc Succinate dehydrogenase misc Histone post-translational modifications misc Mass spectrometry misc SDH misc Cancer predisposition misc Germline pathogenic variant A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide
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topic_title	A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide Phaeochromocytoma (dpeaa)DE-He213 Paraganglioma (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Succinate dehydrogenase (dpeaa)DE-He213 Histone post-translational modifications (dpeaa)DE-He213 Mass spectrometry (dpeaa)DE-He213 SDH (dpeaa)DE-He213 Cancer predisposition (dpeaa)DE-He213 Germline pathogenic variant (dpeaa)DE-He213
topic	misc Phaeochromocytoma misc Paraganglioma misc DNA methylation misc Epigenetics misc Succinate dehydrogenase misc Histone post-translational modifications misc Mass spectrometry misc SDH misc Cancer predisposition misc Germline pathogenic variant
topic_unstemmed	misc Phaeochromocytoma misc Paraganglioma misc DNA methylation misc Epigenetics misc Succinate dehydrogenase misc Histone post-translational modifications misc Mass spectrometry misc SDH misc Cancer predisposition misc Germline pathogenic variant
topic_browse	misc Phaeochromocytoma misc Paraganglioma misc DNA methylation misc Epigenetics misc Succinate dehydrogenase misc Histone post-translational modifications misc Mass spectrometry misc SDH misc Cancer predisposition misc Germline pathogenic variant
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title	A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide
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title_full	A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide
author_sort	Chatzikyriakou, Prodromos
journal	Clinical epigenetics
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author_browse	Chatzikyriakou, Prodromos Brempou, Dimitria Quinn, Mark Fishbein, Lauren Noberini, Roberta Anastopoulos, Ioannis N. Tufton, Nicola Lim, Eugenie S. Obholzer, Rupert Hubbard, Johnathan G. Moonim, Mufaddal Bonaldi, Tiziana Nathanson, Katherine L. Izatt, Louise Oakey, Rebecca J.
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author-letter	Chatzikyriakou, Prodromos
doi_str_mv	10.1186/s13148-023-01598-3
title_sort	comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, dna methylation and transcriptomic analysis genome wide
title_auth	A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide
abstract	Background Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic variants affecting enzymes of the tricarboxylic acid cycle, including succinate dehydrogenase. Within inherited PPGLs, these are the most common. PPGL tumours are known to undergo epigenetic reprograming, and here, we report on global histone post-translational modifications and DNA methylation levels, alongside clinical phenotypes. Results Out of the 25 histone post-translational modifications examined, Cluster 1A PPGLs were distinguished from other tumours by a decrease in hyper-acetylated peptides and an increase in H3K4me2. DNA methylation was compared between tumours from individuals who developed metastatic disease versus those that did not. The majority of differentially methylated sites identified tended to be completely methylated or unmethylated in non-metastatic tumours, with low inter-sample variance. Metastatic tumours by contrast consistently had an intermediate DNA methylation state, including the ephrin receptor EPHA4 and its ligand EFNA3. Gene expression analyses performed to identify genes involved in metastatic tumour behaviour pin-pointed a number of genes previously described as mis-regulated in Cluster 1A tumours, as well as highlighting the tumour suppressor RGS22 and the pituitary tumour-transforming gene PTTG1. Conclusions Combined transcriptomic and DNA methylation analyses revealed aberrant pathways, including ones that could be implicated in metastatic phenotypes and, for the first time, we report a decrease in hyper-acetylated histone marks in Cluster 1 PPGLs. © The Author(s) 2023
abstractGer	Background Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic variants affecting enzymes of the tricarboxylic acid cycle, including succinate dehydrogenase. Within inherited PPGLs, these are the most common. PPGL tumours are known to undergo epigenetic reprograming, and here, we report on global histone post-translational modifications and DNA methylation levels, alongside clinical phenotypes. Results Out of the 25 histone post-translational modifications examined, Cluster 1A PPGLs were distinguished from other tumours by a decrease in hyper-acetylated peptides and an increase in H3K4me2. DNA methylation was compared between tumours from individuals who developed metastatic disease versus those that did not. The majority of differentially methylated sites identified tended to be completely methylated or unmethylated in non-metastatic tumours, with low inter-sample variance. Metastatic tumours by contrast consistently had an intermediate DNA methylation state, including the ephrin receptor EPHA4 and its ligand EFNA3. Gene expression analyses performed to identify genes involved in metastatic tumour behaviour pin-pointed a number of genes previously described as mis-regulated in Cluster 1A tumours, as well as highlighting the tumour suppressor RGS22 and the pituitary tumour-transforming gene PTTG1. Conclusions Combined transcriptomic and DNA methylation analyses revealed aberrant pathways, including ones that could be implicated in metastatic phenotypes and, for the first time, we report a decrease in hyper-acetylated histone marks in Cluster 1 PPGLs. © The Author(s) 2023
abstract_unstemmed	Background Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic variants affecting enzymes of the tricarboxylic acid cycle, including succinate dehydrogenase. Within inherited PPGLs, these are the most common. PPGL tumours are known to undergo epigenetic reprograming, and here, we report on global histone post-translational modifications and DNA methylation levels, alongside clinical phenotypes. Results Out of the 25 histone post-translational modifications examined, Cluster 1A PPGLs were distinguished from other tumours by a decrease in hyper-acetylated peptides and an increase in H3K4me2. DNA methylation was compared between tumours from individuals who developed metastatic disease versus those that did not. The majority of differentially methylated sites identified tended to be completely methylated or unmethylated in non-metastatic tumours, with low inter-sample variance. Metastatic tumours by contrast consistently had an intermediate DNA methylation state, including the ephrin receptor EPHA4 and its ligand EFNA3. Gene expression analyses performed to identify genes involved in metastatic tumour behaviour pin-pointed a number of genes previously described as mis-regulated in Cluster 1A tumours, as well as highlighting the tumour suppressor RGS22 and the pituitary tumour-transforming gene PTTG1. Conclusions Combined transcriptomic and DNA methylation analyses revealed aberrant pathways, including ones that could be implicated in metastatic phenotypes and, for the first time, we report a decrease in hyper-acetylated histone marks in Cluster 1 PPGLs. © The Author(s) 2023
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title_short	A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide
url	https://dx.doi.org/10.1186/s13148-023-01598-3
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author2	Brempou, Dimitria Quinn, Mark Fishbein, Lauren Noberini, Roberta Anastopoulos, Ioannis N. Tufton, Nicola Lim, Eugenie S. Obholzer, Rupert Hubbard, Johnathan G. Moonim, Mufaddal Bonaldi, Tiziana Nathanson, Katherine L. Izatt, Louise Oakey, Rebecca J.
author2Str	Brempou, Dimitria Quinn, Mark Fishbein, Lauren Noberini, Roberta Anastopoulos, Ioannis N. Tufton, Nicola Lim, Eugenie S. Obholzer, Rupert Hubbard, Johnathan G. Moonim, Mufaddal Bonaldi, Tiziana Nathanson, Katherine L. Izatt, Louise Oakey, Rebecca J.
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A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide

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