A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases

Garzia, Livia; Kijima, Noriyuki; Morrissy, A. Sorana; Antonellis, Pasqualino De; Guerreiro-Stucklin, Ana; Holgado, Borja L.; Wu, Xiaochong; Wang, Xin; Parsons, Michael T.; Zayne, Kory; Manno, Alex; Kuzan-Fischer, Claudia M.; Nör, Carolina; Donovan, Laura; Liu, Jessica; Qin, Lei; Garancher, Alexandra; Liu, Kun Wei; Mansouri, Sheila; Luu, Betty; Thompson, Yuan; Ramaswamy, Vijay; Peacock, John; Farooq, Hamza; Skowron, Patryk; Shih, David; Li, Angela; Ensan, Sherine; Robbins, Clinton S.; Cybulsky, Myron I.; Mitra, Siddhartha; Ma, Yussanne; Moore, Richard A.; Mungall, Andrew J.; Cho, Yoon Jae; Weiss, William A.; Chan, Jennifer A.; Hawkins, Cynthia; Massimino, Maura; Jabado, Nada; Zápotocký, Michal; Sumerauer, David; Bouffet, Éric; Dirks, Peter B.; Tabori, Uri; Sorensen, Poul H.; Brastianos, Priscilla K.; Aldape, Kenneth; Jones, Steven J.M.; Marra, Marco A.; Woodgett, James R.; Wechsler‐Reya, Robert J.; Fults, Daniel W.; Taylor, Michael D.

doi:10.1016/j.cell.2018.05.033

Cited by 41 publications

(25 citation statements)

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“…Medulloblastomas exhibit well-characterized intertumoral heterogeneity, as well as geographic, spatial (metastases) and temporal (at recurrence) heterogeneity 1,2,24,35–39 . Cerebellar ependymomas also show marked intertumoral heterogeneity 15–19,26 , while the intertumoral heterogeneity amongst C-PAs is not well characterized 25 .…”

Section: Single-cell Heterogeneity In Cerebellar Tumorsmentioning

confidence: 99%

Childhood cerebellar tumours mirror conserved fetal transcriptional programs

Vladoiu

El-Hamamy

Donovan

et al. 2019

Nature

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Summary: The study of the origin and development of cerebellar tumors has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. We used single-cell transcriptomics to study >60,000 cells from the developing murine cerebellum, and show that different molecular subgroups of childhood cerebellar tumors mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. Sonic Hedgehog medulloblastoma transcriptionally mirrors the granule cell hierarchy as expected, whereas Group3 MB resemble Nestin+ve stem cells, Group 4 MB resemble unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the pre-natal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumors demonstrates that many bulk tumors contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumors as a disorder of early brain development, and provide a proximate explanation for the peak incidence of cerebellar tumors in early childhood.

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Section: Single-cell Heterogeneity In Cerebellar Tumorsmentioning

confidence: 99%

Childhood cerebellar tumours mirror conserved fetal transcriptional programs

Vladoiu

El-Hamamy

Donovan

et al. 2019

Nature

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324

445

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“…Medulloblastomas are known to exhibit well-characterized intertumoral heterogeneity, as well as geographic, spatial (metastases) and temporal (at recurrence) heterogeneity 1,23,25,[36][37][38][39][40] . Posterior fossa (cerebellar) ependymomas also show marked intertumoral heterogeneity [15][16][17][18][19]27 , while the intertumoral heterogeneity amongst cerebellar pilocytic astrocytomas is not well characterized 26 .…”

Section: Single Cell Heterogeneity In Human Cerebellar Tumorsmentioning

confidence: 99%

Childhood Cerebellar Tumors Mirror Conserved Fetal Transcriptional Programs

Vladoiu

El-Hamamy

Donovan

et al. 2018

Preprint

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Summary: 150 wordsThe study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development.We used single-cell transcriptomics to study >60,000 cells from the developing murine All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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“…Therefore, irradiation of the whole brain and spinal cord is recommended as the standard of care for prophylaxis against metastases in all patients older than 3 years. However, this procedure is also a major source of morbidity in survivors, causing significant detrimental effects on intelligence and neurologic and endocrine function, as well as the development of secondary radiation-induced neoplasms [ 102 ]. Clearly, making the leptomeningeal compartment a point of focus for research is warranted to decrease mortality and morbidity in patients with medulloblastoma.…”

Section: Potential Role Of Aptamers In Pediatric Neuro-oncologymentioning

confidence: 99%

Aptamers: Novel Therapeutics and Potential Role in Neuro-Oncology

Amero

Khatua

Rodríguez-Aguayo

et al. 2020

Cancers

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A relatively new paradigm in cancer therapeutics is the use of cancer cell–specific aptamers, both as therapeutic agents and for targeted delivery of anticancer drugs. After the first therapeutic aptamer was described nearly 25 years ago, and the subsequent first aptamer drug approved, many efforts have been made to translate preclinical research into clinical oncology settings. Studies of aptamer-based technology have unveiled the vast potential of aptamers in therapeutic and diagnostic applications. Among pediatric solid cancers, brain tumors are the leading cause of death. Although a few aptamer-related translational studies have been performed in adult glioblastoma, the use of aptamers in pediatric neuro-oncology remains unexplored. This review will discuss the biology of aptamers, including mechanisms of targeting cell surface proteins, various modifications of aptamer structure to enhance therapeutic efficacy, the current state and challenges of aptamer use in neuro-oncology, and the potential therapeutic role of aptamers in pediatric brain tumors.

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A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases

Cited by 41 publications

References 0 publications

Childhood cerebellar tumours mirror conserved fetal transcriptional programs

Childhood cerebellar tumours mirror conserved fetal transcriptional programs

Childhood Cerebellar Tumors Mirror Conserved Fetal Transcriptional Programs

Aptamers: Novel Therapeutics and Potential Role in Neuro-Oncology

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