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Article: Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study

TitleClinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study
Authors
KeywordsPineoblastoma
Pineal parenchymal tumors of intermediate differentiation
DNA methylation profiling
Molecular groups
Consensus
Issue Date2021
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00401/index.htm
Citation
Acta Neuropathologica, 2021, Epub 2021-02-22 How to Cite?
AbstractRecent genomic studies have shed light on the biology and inter-tumoral heterogeneity underlying pineal parenchymal tumors, in particular pineoblastomas (PBs) and pineal parenchymal tumors of intermediate differentiation (PPTIDs). Previous reports, however, had modest sample sizes and lacked the power to integrate molecular and clinical findings. The different proposed molecular group structures also highlighted a need to reach consensus on a robust and relevant classification system. We performed a meta-analysis on 221 patients with molecularly characterized PBs and PPTIDs. DNA methylation profiles were analyzed through complementary bioinformatic approaches and molecular subgrouping was harmonized. Demographic, clinical, and genomic features of patients and samples from these pineal tumor groups were annotated. Four clinically and biologically relevant consensus PB groups were defined: PB-miRNA1 (n = 96), PB-miRNA2 (n = 23), PB-MYC/FOXR2 (n = 34), and PB-RB1 (n = 25). A final molecularly distinct group, designated PPTID (n = 43), comprised histological PPTID and PBs. Genomic and transcriptomic profiling allowed the characterization of oncogenic drivers for individual tumor groups, specifically, alterations in the microRNA processing pathway in PB-miRNA1/2, MYC amplification and FOXR2 overexpression in PB-MYC/FOXR2, RB1 alteration in PB-RB1, and KBTBD4 insertion in PPTID. Age at diagnosis, sex predilection, and metastatic status varied significantly among tumor groups. While patients with PB-miRNA2 and PPTID had superior outcome, survival was intermediate for patients with PB-miRNA1, and dismal for those with PB-MYC/FOXR2 or PB-RB1. Reduced-dose CSI was adequate for patients with average-risk, PB-miRNA1/2 disease. We systematically interrogated the clinical and molecular heterogeneity within pineal parenchymal tumors and proposed a consensus nomenclature for disease groups, laying the groundwork for future studies as well as routine use in tumor diagnostic classification and clinical trial stratification.
Persistent Identifierhttp://hdl.handle.net/10722/288131
ISSN
2019 Impact Factor: 14.251
2015 SCImago Journal Rankings: 6.610

 

DC FieldValueLanguage
dc.contributor.authorLiu, APY-
dc.contributor.authorLi, BK-
dc.contributor.authorPfaff, E-
dc.contributor.authorGudenas, B-
dc.contributor.authorVasiljevic, A-
dc.contributor.authorOrr, BA-
dc.contributor.authorDufour, C-
dc.contributor.authorSnuderl, M-
dc.contributor.authorKarajannis, MA-
dc.contributor.authorRosenblum, MK-
dc.contributor.authorHwang, EI-
dc.contributor.authorNg, HK-
dc.contributor.authorHansford, JR-
dc.contributor.authorSzathmari, A-
dc.contributor.authorFaure-Conter, C-
dc.contributor.authorMerchant, TE-
dc.contributor.authorLevine, M-
dc.contributor.authorBouvier, N-
dc.contributor.authorvon Hoff, K-
dc.contributor.authorMynarck, M-
dc.contributor.authorRutkowski, S-
dc.contributor.authorSahm, F-
dc.contributor.authorKool, M-
dc.contributor.authorHawkins, C-
dc.contributor.authorOnar-Thomas, A-
dc.contributor.authorRobinson, GW-
dc.contributor.authorGajjar, A-
dc.contributor.authorPfister, SM-
dc.contributor.authorBouffet, E-
dc.contributor.authorNorthcott, PA-
dc.contributor.authorJones, DTW-
dc.contributor.authorHuang, A-
dc.date.accessioned2020-10-05T12:08:19Z-
dc.date.available2020-10-05T12:08:19Z-
dc.date.issued2021-
dc.identifier.citationActa Neuropathologica, 2021, Epub 2021-02-22-
dc.identifier.issn0001-6322-
dc.identifier.urihttp://hdl.handle.net/10722/288131-
dc.description.abstractRecent genomic studies have shed light on the biology and inter-tumoral heterogeneity underlying pineal parenchymal tumors, in particular pineoblastomas (PBs) and pineal parenchymal tumors of intermediate differentiation (PPTIDs). Previous reports, however, had modest sample sizes and lacked the power to integrate molecular and clinical findings. The different proposed molecular group structures also highlighted a need to reach consensus on a robust and relevant classification system. We performed a meta-analysis on 221 patients with molecularly characterized PBs and PPTIDs. DNA methylation profiles were analyzed through complementary bioinformatic approaches and molecular subgrouping was harmonized. Demographic, clinical, and genomic features of patients and samples from these pineal tumor groups were annotated. Four clinically and biologically relevant consensus PB groups were defined: PB-miRNA1 (n = 96), PB-miRNA2 (n = 23), PB-MYC/FOXR2 (n = 34), and PB-RB1 (n = 25). A final molecularly distinct group, designated PPTID (n = 43), comprised histological PPTID and PBs. Genomic and transcriptomic profiling allowed the characterization of oncogenic drivers for individual tumor groups, specifically, alterations in the microRNA processing pathway in PB-miRNA1/2, MYC amplification and FOXR2 overexpression in PB-MYC/FOXR2, RB1 alteration in PB-RB1, and KBTBD4 insertion in PPTID. Age at diagnosis, sex predilection, and metastatic status varied significantly among tumor groups. While patients with PB-miRNA2 and PPTID had superior outcome, survival was intermediate for patients with PB-miRNA1, and dismal for those with PB-MYC/FOXR2 or PB-RB1. Reduced-dose CSI was adequate for patients with average-risk, PB-miRNA1/2 disease. We systematically interrogated the clinical and molecular heterogeneity within pineal parenchymal tumors and proposed a consensus nomenclature for disease groups, laying the groundwork for future studies as well as routine use in tumor diagnostic classification and clinical trial stratification.-
dc.languageeng-
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00401/index.htm-
dc.relation.ispartofActa Neuropathologica-
dc.rightsThis is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: https://doi.org/[insert DOI]-
dc.subjectPineoblastoma-
dc.subjectPineal parenchymal tumors of intermediate differentiation-
dc.subjectDNA methylation profiling-
dc.subjectMolecular groups-
dc.subjectConsensus-
dc.titleClinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study-
dc.typeArticle-
dc.identifier.emailLiu, APY: apyliu@hku.hk-
dc.identifier.authorityLiu, APY=rp01357-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00401-021-02284-5-
dc.identifier.pmid33619588-
dc.identifier.scopuseid_2-s2.0-85101224550-
dc.identifier.hkuros315657-
dc.identifier.volumeEpub 2021-02-22-
dc.publisher.placeGermany-
dc.identifier.issnl0001-6322-

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