| Literature DB >> 33741928 |
Patryk Skowron1,2,3, Hamza Farooq1,2,3, Florence M G Cavalli1,3, A Sorana Morrissy4,5,6, Michelle Ly1,2,3, Liam D Hendrikse1,3,7, Evan Y Wang1,3,7, Haig Djambazian8,9, Helen Zhu7,10, Karen L Mungall11, Quang M Trinh10, Tina Zheng12, Shizhong Dai13, Ana S Guerreiro Stucklin1,3, Maria C Vladoiu1,2,3, Vernon Fong1,3, Borja L Holgado1,3, Carolina Nor1,3, Xiaochong Wu1,3, Diala Abd-Rabbo10, Pierre Bérubé8, Yu Chang Wang8, Betty Luu1,3, Raul A Suarez1,3, Avesta Rastan1,3,14, Aaron H Gillmor4,5,6, John J Y Lee1,2,3, Xiao Yun Zhang1, Craig Daniels1,3, Peter Dirks1,3,15,16, David Malkin7,17, Eric Bouffet3,17, Uri Tabori3,14,17, James Loukides3, François P Doz18, Franck Bourdeaut18, Olivier O Delattre19, Julien Masliah-Planchon20, Olivier Ayrault21, Seung-Ki Kim22, David Meyronet23, Wieslawa A Grajkowska24, Carlos G Carlotti25, Carmen de Torres26, Jaume Mora26, Charles G Eberhart27, Erwin G Van Meir28, Toshihiro Kumabe29, Pim J French30, Johan M Kros31, Nada Jabado32, Boleslaw Lach33,34, Ian F Pollack35, Ronald L Hamilton36, Amulya A Nageswara Rao37, Caterina Giannini38, James M Olson39, László Bognár40, Almos Klekner40, Karel Zitterbart41, Joanna J Phillips42,43, Reid C Thompson44, Michael K Cooper45, Joshua B Rubin46, Linda M Liau47, Miklós Garami48, Peter Hauser48, Kay Ka Wai Li49, Ho-Keung Ng49, Wai Sang Poon50, G Yancey Gillespie51, Jennifer A Chan6, Shin Jung52, Roger E McLendon53,54, Eric M Thompson54, David Zagzag55, Rajeev Vibhakar56, Young Shin Ra57, Maria Luisa Garre58, Ulrich Schüller59,60,61, Tomoko Shofuda62, Claudia C Faria63,64, Enrique López-Aguilar65, Gelareh Zadeh66,67, Chi-Chung Hui1,16, Vijay Ramaswamy1,3,7,17, Swneke D Bailey68,69, Steven J Jones11,70,71, Andrew J Mungall11, Richard A Moore11, John A Calarco72, Lincoln D Stein16,73, Gary D Bader16,74, Jüri Reimand7,10,16, Jiannis Ragoussis8,9, William A Weiss12,42,75, Marco A Marra11,70, Hiromichi Suzuki76,77, Michael D Taylor78,79,80,81,82,83.
Abstract
Sonic 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 on GLI2 activity 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 encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. 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.Entities:
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Year: 2021 PMID： 33741928 PMCID： PMC7979819 DOI： 10.1038/s41467-021-21883-0
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 17.694