The transcriptional landscape of Shh medulloblastoma
-
Published:2021-03-19
Issue:1
Volume:12
Page:
-
ISSN:2041-1723
-
Container-title:Nature Communications
-
language:en
-
Short-container-title:Nat Commun
Author:
Skowron Patryk, Farooq Hamza, Cavalli Florence M. G., Morrissy A. Sorana, Ly Michelle, Hendrikse Liam D.ORCID, Wang Evan Y.ORCID, Djambazian HaigORCID, Zhu Helen, Mungall Karen L., Trinh Quang M.ORCID, Zheng Tina, Dai Shizhong, Stucklin Ana S. GuerreiroORCID, Vladoiu Maria C., Fong VernonORCID, Holgado Borja L., Nor Carolina, Wu Xiaochong, Abd-Rabbo Diala, Bérubé PierreORCID, Wang Yu Chang, Luu Betty, Suarez Raul A., Rastan AvestaORCID, Gillmor Aaron H., Lee John J. Y., Zhang Xiao Yun, Daniels Craig, Dirks PeterORCID, Malkin DavidORCID, Bouffet Eric, Tabori Uri, Loukides James, Doz François P., Bourdeaut Franck, Delattre Olivier O.ORCID, Masliah-Planchon Julien, Ayrault OlivierORCID, Kim Seung-Ki, Meyronet David, Grajkowska Wieslawa A., Carlotti Carlos G., de Torres Carmen, Mora Jaume, Eberhart Charles G., Van Meir Erwin G., Kumabe Toshihiro, French Pim J.ORCID, Kros Johan M., Jabado NadaORCID, Lach Boleslaw, Pollack Ian F., Hamilton Ronald L., Rao Amulya A. Nageswara, Giannini CaterinaORCID, Olson James M., Bognár László, Klekner Almos, Zitterbart Karel, Phillips Joanna J.ORCID, Thompson Reid C., Cooper Michael K., Rubin Joshua B.ORCID, Liau Linda M.ORCID, Garami MiklósORCID, Hauser Peter, Li Kay Ka Wai, Ng Ho-Keung, Poon Wai Sang, Yancey Gillespie G., Chan Jennifer A., Jung Shin, McLendon Roger E., Thompson Eric M., Zagzag David, Vibhakar Rajeev, Ra Young Shin, Garre Maria Luisa, Schüller UlrichORCID, Shofuda Tomoko, Faria Claudia C., López-Aguilar Enrique, Zadeh Gelareh, Hui Chi-Chung, Ramaswamy VijayORCID, Bailey Swneke D., Jones Steven J.ORCID, Mungall Andrew J.ORCID, Moore Richard A., Calarco John A., Stein Lincoln D., Bader Gary D.ORCID, Reimand JüriORCID, Ragoussis JiannisORCID, Weiss William A., Marra Marco A.ORCID, Suzuki HiromichiORCID, Taylor Michael D.ORCID
Abstract
AbstractSonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS,PRKAR1A) which converge onGLI2activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassingGLI2, and several loss-of-function fusions in tumor suppressor genesPTCH1,SUFUandNCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference69 articles.
1. Stucklin, A. S. G., Ramaswamy, V., Daniels, C. & Taylor, M. D. Review of molecular classification and treatment implications of pediatric brain tumors. Curr. Opin. Pediatr. 30, 3–9 (2018). 2. Taylor, M. D. et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 123, 465–472 (2012). 3. Cavalli, F. M. G. et al. Intertumoral heterogeneity within medulloblastoma subgroups. Cancer Cell 31, 737–754.e6 (2017). 4. Suzuki, H. et al. Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma. Nature 574, 707–711 (2019). 5. He, X. et al. The G protein α subunit Gαs is a tumor suppressor in Sonic hedgehog−driven medulloblastoma. Nat. Med. 20, 1035–1042 (2014).
Cited by
55 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|