Year: 2019
Type: conference-abstract
Abstract: Medulloblastoma is a malignant childhood cerebellar tumor comprised of distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. We used single-cell transcriptomics to investigate intra- and inter-tumoral heterogeneity in twenty-five medulloblastomas spanning all molecular subgroups. WNT, SHH, and Group 3 tumors comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumors were exclusively comprised of differentiated neuronal-like neoplastic cells. SHH tumors closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumors exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, whose relative proportions distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide novel insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.
Source: Neuro-Oncology
Authors: Laure Bihannic, Volker Hovestadt, Kyle Smith, Mariella Filbin, McKenzie Shaw, Alicia Baumgartner, John DeWitt, Andrew Groves, Lisa Mayr, Hannah Weisman, Alyssa Richman, Marni Shore, Liliana Goumnerova, Celeste Rosencrance, Robert Carter, Timothy Phoenix, Jennifer Hadley, Yiai Tong, Jim Houston, Richard Ashmun, Michael DeCuypere, Tanvi Sharma, Keith Ligon, Scott Pomeroy, Miguel Rivera, Orit Rozenblatt-Rosen, Jessica Rusert, Robert Wechsler-Reya, Xiao-Nan Li, Andreas Peyrl, Johannes Gojo, Dominik Kirchhofer, Daniela Lötsch, Thomas Czech, Christian Dorfer, Christine Haberler, Rene Geyeregger, Angela Halfmann, Charles Gawad, John Easton, Stefan Pfister, Aviv Regev, Amar Gajjar, Brent Orr, Irene Slavc, Giles Robinson, Bradley Bernstein, Mario Suvà, Paul Northcott
Institutions: St. Jude Children's Research Hospital, Broad Institute, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Medical University of Vienna, Hopp Children's Cancer Center Heidelberg, Harvard University, Sanford Burnham Prebys Medical Discovery Institute, Lurie Children's Hospital, St. Anna Children's Cancer Research Institute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2983061380