GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma-Reference-Cited by-同舟云学术

GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma

Published:2021-01-18 Issue:2 Volume:80 Page:129-136
ISSN:0022-3069
Container-title:Journal of Neuropathology & Experimental Neurology
language:en
Short-container-title:

Author:

Natsumeda Manabu¹,Miyahara Hiroaki²³,Yoshimura Junichi¹,Nakata Satoshi⁴,Nozawa Takanori¹,Ito Junko¹⁵,Kanemaru Yu¹,Watanabe Jun¹,Tsukamoto Yoshihiro¹,Okada Masayasu¹,Oishi Makoto¹,Hirato Junko⁶⁷,Wataya Takafumi⁷,Ahsan Sama⁴,Tateishi Kensuke⁸,Yamamoto Tetsuya⁸,Rodriguez Fausto J⁴,Takahashi Hitoshi⁵,Hovestadt Volker⁹¹⁰,Suva Mario L⁹¹⁰,Taylor Michael D¹¹,Eberhart Charles G¹¹,Fujii Yukihiko¹,Kakita Akiyoshi⁵

Affiliation:

1. From the Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan

2. Department of Pediatrics, Oita University Faculty of Medicine, Yufu, Japan

3. Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Japan

4. Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland

5. Department of Pathology, Brain Research Institute, Niigata University

6. Department of Pathology, Public Tomioka General Hospital, Tomioka, Japan

7. Department of Human Pathology, Gunma University, Maebashi, Japan

8. Department of Neurosurgery, Yokohama City University, Yokohama, Japan

9. Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusettes

10. Broad Institute of Harvard and MIT, Cambridge, Massachusettes

11. Department of Neurosurgery, Hospital for Sick Children, Toronto, Canada

Abstract

Abstract Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.

Funder

Japan-US Brain Research Cooperation Program

Publisher

Oxford University Press (OUP)

Subject

Cellular and Molecular Neuroscience,Clinical Neurology,Neurology,General Medicine,Pathology and Forensic Medicine

Link

http://academic.oup.com/jnen/article-pdf/80/2/129/35933249/nlaa141.pdf

Reference25 articles.

1. Medulloblastoma comprises four distinct molecular variants;Northcott;J Clin Oncol,2011

2. Intertumoral heterogeneity within medulloblastoma subgroups;Cavalli;Cancer Cell,2017

3. Sonic hedgehog differentially regulates expression of Gli and Gli3 during limb development;Marigo;Dev Biol,1996