DNA methylation signature is prognostic of choroid plexus tumor aggressiveness

Background Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Pienkowska, Malgorzata [verfasserIn] Choufani, Sanaa Turinsky, Andrei L. Guha, Tanya Merino, Diana M. Novokmet, Ana Brudno, Michael Weksberg, Rosanna Shlien, Adam Hawkins, Cynthia Bouffet, Eric Tabori, Uri Gilbertson, Richard J. Finlay, Jonathan L. Jabado, Nada Thomas, Christian Sill, Martin Capper, David Hasselblatt, Martin Malkin, David

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	DNA methylation Choroid plexus tumors HumanMethylation450 arrays Quantitative sodium bisulfite pyrosequencing

Anmerkung:	© The Author(s). 2019. corrected publication 2019

Übergeordnetes Werk:	Enthalten in: Clinical epigenetics - [S.l.] : BioMed Central, 2010, 11(2019), 1 vom: 13. Aug.
Übergeordnetes Werk:	volume:11 ; year:2019 ; number:1 ; day:13 ; month:08

Links:	Volltext

DOI / URN:	10.1186/s13148-019-0708-z

Katalog-ID:	SPR030678846

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520			\|a Background Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management.
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allfields	10.1186/s13148-019-0708-z doi (DE-627)SPR030678846 (SPR)s13148-019-0708-z-e DE-627 ger DE-627 rakwb eng Pienkowska, Malgorzata verfasserin aut DNA methylation signature is prognostic of choroid plexus tumor aggressiveness 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019. corrected publication 2019 Background Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management. DNA methylation (dpeaa)DE-He213 Choroid plexus tumors (dpeaa)DE-He213 HumanMethylation450 arrays (dpeaa)DE-He213 Quantitative sodium bisulfite pyrosequencing (dpeaa)DE-He213 Choufani, Sanaa aut Turinsky, Andrei L. aut Guha, Tanya aut Merino, Diana M. aut Novokmet, Ana aut Brudno, Michael aut Weksberg, Rosanna aut Shlien, Adam aut Hawkins, Cynthia aut Bouffet, Eric aut Tabori, Uri aut Gilbertson, Richard J. aut Finlay, Jonathan L. aut Jabado, Nada aut Thomas, Christian aut Sill, Martin aut Capper, David aut Hasselblatt, Martin aut Malkin, David (orcid)0000-0001-5752-9763 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 11(2019), 1 vom: 13. Aug. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:11 year:2019 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13148-019-0708-z 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_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 11 2019 1 13 08
spelling	10.1186/s13148-019-0708-z doi (DE-627)SPR030678846 (SPR)s13148-019-0708-z-e DE-627 ger DE-627 rakwb eng Pienkowska, Malgorzata verfasserin aut DNA methylation signature is prognostic of choroid plexus tumor aggressiveness 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019. corrected publication 2019 Background Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management. DNA methylation (dpeaa)DE-He213 Choroid plexus tumors (dpeaa)DE-He213 HumanMethylation450 arrays (dpeaa)DE-He213 Quantitative sodium bisulfite pyrosequencing (dpeaa)DE-He213 Choufani, Sanaa aut Turinsky, Andrei L. aut Guha, Tanya aut Merino, Diana M. aut Novokmet, Ana aut Brudno, Michael aut Weksberg, Rosanna aut Shlien, Adam aut Hawkins, Cynthia aut Bouffet, Eric aut Tabori, Uri aut Gilbertson, Richard J. aut Finlay, Jonathan L. aut Jabado, Nada aut Thomas, Christian aut Sill, Martin aut Capper, David aut Hasselblatt, Martin aut Malkin, David (orcid)0000-0001-5752-9763 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 11(2019), 1 vom: 13. Aug. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:11 year:2019 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13148-019-0708-z 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_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 11 2019 1 13 08
allfields_unstemmed	10.1186/s13148-019-0708-z doi (DE-627)SPR030678846 (SPR)s13148-019-0708-z-e DE-627 ger DE-627 rakwb eng Pienkowska, Malgorzata verfasserin aut DNA methylation signature is prognostic of choroid plexus tumor aggressiveness 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019. corrected publication 2019 Background Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management. DNA methylation (dpeaa)DE-He213 Choroid plexus tumors (dpeaa)DE-He213 HumanMethylation450 arrays (dpeaa)DE-He213 Quantitative sodium bisulfite pyrosequencing (dpeaa)DE-He213 Choufani, Sanaa aut Turinsky, Andrei L. aut Guha, Tanya aut Merino, Diana M. aut Novokmet, Ana aut Brudno, Michael aut Weksberg, Rosanna aut Shlien, Adam aut Hawkins, Cynthia aut Bouffet, Eric aut Tabori, Uri aut Gilbertson, Richard J. aut Finlay, Jonathan L. aut Jabado, Nada aut Thomas, Christian aut Sill, Martin aut Capper, David aut Hasselblatt, Martin aut Malkin, David (orcid)0000-0001-5752-9763 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 11(2019), 1 vom: 13. Aug. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:11 year:2019 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13148-019-0708-z 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_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 11 2019 1 13 08
allfieldsGer	10.1186/s13148-019-0708-z doi (DE-627)SPR030678846 (SPR)s13148-019-0708-z-e DE-627 ger DE-627 rakwb eng Pienkowska, Malgorzata verfasserin aut DNA methylation signature is prognostic of choroid plexus tumor aggressiveness 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019. corrected publication 2019 Background Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management. DNA methylation (dpeaa)DE-He213 Choroid plexus tumors (dpeaa)DE-He213 HumanMethylation450 arrays (dpeaa)DE-He213 Quantitative sodium bisulfite pyrosequencing (dpeaa)DE-He213 Choufani, Sanaa aut Turinsky, Andrei L. aut Guha, Tanya aut Merino, Diana M. aut Novokmet, Ana aut Brudno, Michael aut Weksberg, Rosanna aut Shlien, Adam aut Hawkins, Cynthia aut Bouffet, Eric aut Tabori, Uri aut Gilbertson, Richard J. aut Finlay, Jonathan L. aut Jabado, Nada aut Thomas, Christian aut Sill, Martin aut Capper, David aut Hasselblatt, Martin aut Malkin, David (orcid)0000-0001-5752-9763 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 11(2019), 1 vom: 13. Aug. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:11 year:2019 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13148-019-0708-z 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_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 11 2019 1 13 08
allfieldsSound	10.1186/s13148-019-0708-z doi (DE-627)SPR030678846 (SPR)s13148-019-0708-z-e DE-627 ger DE-627 rakwb eng Pienkowska, Malgorzata verfasserin aut DNA methylation signature is prognostic of choroid plexus tumor aggressiveness 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019. corrected publication 2019 Background Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management. DNA methylation (dpeaa)DE-He213 Choroid plexus tumors (dpeaa)DE-He213 HumanMethylation450 arrays (dpeaa)DE-He213 Quantitative sodium bisulfite pyrosequencing (dpeaa)DE-He213 Choufani, Sanaa aut Turinsky, Andrei L. aut Guha, Tanya aut Merino, Diana M. aut Novokmet, Ana aut Brudno, Michael aut Weksberg, Rosanna aut Shlien, Adam aut Hawkins, Cynthia aut Bouffet, Eric aut Tabori, Uri aut Gilbertson, Richard J. aut Finlay, Jonathan L. aut Jabado, Nada aut Thomas, Christian aut Sill, Martin aut Capper, David aut Hasselblatt, Martin aut Malkin, David (orcid)0000-0001-5752-9763 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 11(2019), 1 vom: 13. Aug. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:11 year:2019 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13148-019-0708-z 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_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 11 2019 1 13 08
language	English
source	Enthalten in Clinical epigenetics 11(2019), 1 vom: 13. Aug. volume:11 year:2019 number:1 day:13 month:08
sourceStr	Enthalten in Clinical epigenetics 11(2019), 1 vom: 13. Aug. volume:11 year:2019 number:1 day:13 month:08
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	DNA methylation Choroid plexus tumors HumanMethylation450 arrays Quantitative sodium bisulfite pyrosequencing
isfreeaccess_bool	true
container_title	Clinical epigenetics
authorswithroles_txt_mv	Pienkowska, Malgorzata @@aut@@ Choufani, Sanaa @@aut@@ Turinsky, Andrei L. @@aut@@ Guha, Tanya @@aut@@ Merino, Diana M. @@aut@@ Novokmet, Ana @@aut@@ Brudno, Michael @@aut@@ Weksberg, Rosanna @@aut@@ Shlien, Adam @@aut@@ Hawkins, Cynthia @@aut@@ Bouffet, Eric @@aut@@ Tabori, Uri @@aut@@ Gilbertson, Richard J. @@aut@@ Finlay, Jonathan L. @@aut@@ Jabado, Nada @@aut@@ Thomas, Christian @@aut@@ Sill, Martin @@aut@@ Capper, David @@aut@@ Hasselblatt, Martin @@aut@@ Malkin, David @@aut@@
publishDateDaySort_date	2019-08-13T00:00:00Z
hierarchy_top_id	626459028
id	SPR030678846
language_de	englisch
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Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. 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author	Pienkowska, Malgorzata
spellingShingle	Pienkowska, Malgorzata misc DNA methylation misc Choroid plexus tumors misc HumanMethylation450 arrays misc Quantitative sodium bisulfite pyrosequencing DNA methylation signature is prognostic of choroid plexus tumor aggressiveness
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topic_title	DNA methylation signature is prognostic of choroid plexus tumor aggressiveness DNA methylation (dpeaa)DE-He213 Choroid plexus tumors (dpeaa)DE-He213 HumanMethylation450 arrays (dpeaa)DE-He213 Quantitative sodium bisulfite pyrosequencing (dpeaa)DE-He213
topic	misc DNA methylation misc Choroid plexus tumors misc HumanMethylation450 arrays misc Quantitative sodium bisulfite pyrosequencing
topic_unstemmed	misc DNA methylation misc Choroid plexus tumors misc HumanMethylation450 arrays misc Quantitative sodium bisulfite pyrosequencing
topic_browse	misc DNA methylation misc Choroid plexus tumors misc HumanMethylation450 arrays misc Quantitative sodium bisulfite pyrosequencing
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title	DNA methylation signature is prognostic of choroid plexus tumor aggressiveness
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title_full	DNA methylation signature is prognostic of choroid plexus tumor aggressiveness
author_sort	Pienkowska, Malgorzata
journal	Clinical epigenetics
journalStr	Clinical epigenetics
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author_browse	Pienkowska, Malgorzata Choufani, Sanaa Turinsky, Andrei L. Guha, Tanya Merino, Diana M. Novokmet, Ana Brudno, Michael Weksberg, Rosanna Shlien, Adam Hawkins, Cynthia Bouffet, Eric Tabori, Uri Gilbertson, Richard J. Finlay, Jonathan L. Jabado, Nada Thomas, Christian Sill, Martin Capper, David Hasselblatt, Martin Malkin, David
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author-letter	Pienkowska, Malgorzata
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title_sort	dna methylation signature is prognostic of choroid plexus tumor aggressiveness
title_auth	DNA methylation signature is prognostic of choroid plexus tumor aggressiveness
abstract	Background Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management. © The Author(s). 2019. corrected publication 2019
abstractGer	Background Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management. © The Author(s). 2019. corrected publication 2019
abstract_unstemmed	Background Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management. © The Author(s). 2019. corrected publication 2019
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title_short	DNA methylation signature is prognostic of choroid plexus tumor aggressiveness
url	https://dx.doi.org/10.1186/s13148-019-0708-z
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author2	Choufani, Sanaa Turinsky, Andrei L. Guha, Tanya Merino, Diana M. Novokmet, Ana Brudno, Michael Weksberg, Rosanna Shlien, Adam Hawkins, Cynthia Bouffet, Eric Tabori, Uri Gilbertson, Richard J. Finlay, Jonathan L. Jabado, Nada Thomas, Christian Sill, Martin Capper, David Hasselblatt, Martin Malkin, David
author2Str	Choufani, Sanaa Turinsky, Andrei L. Guha, Tanya Merino, Diana M. Novokmet, Ana Brudno, Michael Weksberg, Rosanna Shlien, Adam Hawkins, Cynthia Bouffet, Eric Tabori, Uri Gilbertson, Richard J. Finlay, Jonathan L. Jabado, Nada Thomas, Christian Sill, Martin Capper, David Hasselblatt, Martin Malkin, David
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DNA methylation signature is prognostic of choroid plexus tumor aggressiveness

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