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Conference Paper: Dissecting the molecular and developmental basis of pineoblastoma through genomics

TitleDissecting the molecular and developmental basis of pineoblastoma through genomics
Authors
Keywordstranscription
genetic
mutation
heterogeneity
cell nucleus
Issue Date2020
PublisherOxford University Press. The Journal's web site is located at https://academic.oup.com/neuro-oncology
Citation
The 19th International Symposium on Pediatric Neuro-Oncology (ISPNO) 2020, Karuizawa, Japan, 13-16 December 2020. In Neuro-Oncology, 2020, v. 22 n. Suppl. 3, p. iii323–iii324 How to Cite?
AbstractPineoblastoma (PB) is an aggressive embryonal brain tumor comprising 1% of pediatric CNS tumors. The clinico-molecular heterogeneity and developmental origins underlying PB are poorly understood; therefore, we have assembled a molecular cohort of histologically defined PBs (n=43) with corresponding outcome data. Methylation profiling revealed four molecularly and clinically distinct PB subgroups, including two novel entities. Mutational and transcriptional analysis identified characteristic molecular features of each subgroup, such as mutations in the miRNA processing pathway or FOXR2 proto-oncogene overexpression. Furthermore, subgroups exhibited differences in propensity for metastasis, cytogenetics, and clinical outcomes. To dissect PB developmental origins and resolve PB subgroup biology, we have employed a combination of single-cell genomics and genetically engineered mouse modeling. We created a single-cell transcriptional atlas of the developing murine pineal gland across 11 timepoints and are currently integrating these data with single nuclei RNA-seq data of human PB (n=25). Single-cell analysis of the developing pineal gland revealed three distinct populations of pinealocytes, referred to as early, mid and late pinealocytes, which segregate by developmental stage yet lie along a single developmental trajectory. Preliminary results implicate significant associations between PBs and the early pinealocyte population as well as subgroup-specific differences in intratumoral heterogeneity. Furthermore, this knowledge has informed the downstream generation of biologically faithful disease models, including a transgenic mouse model of the PB-RB subgroup. Remarkably, this model shows up-regulation of key markers of PB such as Crx, Asmt and Otx2 and substantiates early pinealocytes as the probable cell-of-origin for this PB subgroup.
DescriptionOoral presentation - Section: ETMR and other Embryonal Tumors - ETMR-06
Persistent Identifierhttp://hdl.handle.net/10722/288270
ISSN
2019 Impact Factor: 10.247
2015 SCImago Journal Rankings: 3.196

 

DC FieldValueLanguage
dc.contributor.authorGudenas, G-
dc.contributor.authorEnglinger, B-
dc.contributor.authorLiu, APY-
dc.contributor.authorTong, Y-
dc.contributor.authorMeredith, D-
dc.contributor.authorPfaff, E-
dc.contributor.authorLin, T-
dc.contributor.authorOrr, BA-
dc.contributor.authorKlimo Jr, P-
dc.contributor.authorBihannic, L-
dc.contributor.authorPaul, L-
dc.contributor.authorKumar, R-
dc.contributor.authorBouffet, E-
dc.contributor.authorGururangan, S-
dc.contributor.authorCrawford, JR-
dc.contributor.authorKellie, SJ-
dc.contributor.authorChintagumpala, M-
dc.contributor.authorFisher, MJ-
dc.contributor.authorBowers, DC-
dc.contributor.authorHassall, T-
dc.contributor.authorIndelicato, DJ-
dc.contributor.authorEllison, DW-
dc.contributor.authorBoop, FA-
dc.contributor.authorMerchant, TE-
dc.contributor.authorChiang, J-
dc.contributor.authorRobinson, GW-
dc.contributor.authorGajjar, A-
dc.contributor.authorAlexandrescu, S-
dc.contributor.authorJones, DTW-
dc.contributor.authorFilbin, MG-
dc.contributor.authorNorthcott, PA-
dc.date.accessioned2020-10-05T12:10:24Z-
dc.date.available2020-10-05T12:10:24Z-
dc.date.issued2020-
dc.identifier.citationThe 19th International Symposium on Pediatric Neuro-Oncology (ISPNO) 2020, Karuizawa, Japan, 13-16 December 2020. In Neuro-Oncology, 2020, v. 22 n. Suppl. 3, p. iii323–iii324-
dc.identifier.issn1522-8517-
dc.identifier.urihttp://hdl.handle.net/10722/288270-
dc.descriptionOoral presentation - Section: ETMR and other Embryonal Tumors - ETMR-06-
dc.description.abstractPineoblastoma (PB) is an aggressive embryonal brain tumor comprising 1% of pediatric CNS tumors. The clinico-molecular heterogeneity and developmental origins underlying PB are poorly understood; therefore, we have assembled a molecular cohort of histologically defined PBs (n=43) with corresponding outcome data. Methylation profiling revealed four molecularly and clinically distinct PB subgroups, including two novel entities. Mutational and transcriptional analysis identified characteristic molecular features of each subgroup, such as mutations in the miRNA processing pathway or FOXR2 proto-oncogene overexpression. Furthermore, subgroups exhibited differences in propensity for metastasis, cytogenetics, and clinical outcomes. To dissect PB developmental origins and resolve PB subgroup biology, we have employed a combination of single-cell genomics and genetically engineered mouse modeling. We created a single-cell transcriptional atlas of the developing murine pineal gland across 11 timepoints and are currently integrating these data with single nuclei RNA-seq data of human PB (n=25). Single-cell analysis of the developing pineal gland revealed three distinct populations of pinealocytes, referred to as early, mid and late pinealocytes, which segregate by developmental stage yet lie along a single developmental trajectory. Preliminary results implicate significant associations between PBs and the early pinealocyte population as well as subgroup-specific differences in intratumoral heterogeneity. Furthermore, this knowledge has informed the downstream generation of biologically faithful disease models, including a transgenic mouse model of the PB-RB subgroup. Remarkably, this model shows up-regulation of key markers of PB such as Crx, Asmt and Otx2 and substantiates early pinealocytes as the probable cell-of-origin for this PB subgroup.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at https://academic.oup.com/neuro-oncology-
dc.relation.ispartofNeuro-Oncology-
dc.relation.ispartofThe 19th International Symposium on Pediatric Neuro-Oncology (ISPNO) 2020-
dc.subjecttranscription-
dc.subjectgenetic-
dc.subjectmutation-
dc.subjectheterogeneity-
dc.subjectcell nucleus-
dc.titleDissecting the molecular and developmental basis of pineoblastoma through genomics-
dc.typeConference_Paper-
dc.identifier.emailLiu, APY: apyliu@hku.hk-
dc.identifier.authorityLiu, APY=rp01357-
dc.description.natureabstract-
dc.identifier.doi10.1093/neuonc/noaa222.210-
dc.identifier.hkuros314989-
dc.identifier.volume22-
dc.identifier.issueSuppl. 3-
dc.identifier.spageiii323-
dc.identifier.epageiii324-
dc.publisher.placeUnited States-

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