The transcriptional landscape of Shh medulloblastoma

• DOI: 10.1038/s41467-021-21883-0
• Publication Date: 2021-03-19T13:05:27Z
• Authors: Patryk Skowron; Hamza Farooq; Florence M. G. Ca...; A. Sorana Morrissy; Michelle Ly; Liam D. Hendrikse; Evan Y. Wang; Haig Djambazian; Helen Zhu; Karen L. Mungall; Quang M. Trinh; Tina Zheng; Shizhong Dai; Ana S. Guerreiro ...; Maria C. Vladoiu; Vernon Fong; Borja L. Holgado; Carolina Nor; Xiaochong Wu; Diala Abd-Rabbo; Pierre Bérubé; Yu Chang Wang; Betty Luu; Raul A. Suarez; Avesta Rastan; Aaron H. Gillmor; John J. Y. Lee; Xiao Yun Zhang; Craig Daniels; Peter Dirks; David Malkin; Eric Bouffet; Uri Tabori; James Loukides; François P. Doz; Franck Bourdeaut; Olivier O. Delattre; Julien Masliah-Pl...; Olivier Ayrault; Seung-Ki Kim; David Meyronet; Wieslawa A. Grajk...; Carlos G. Carlotti; Carmen de Torres; Jaume Mora; Charles G. Eberhart; Erwin G. Van Meir; Toshihiro Kumabe; Pim J. French; Johan M. Kros; Nada Jabado; Boleslaw Lach; Ian F. Pollack; Ronald L. Hamilton; Amulya A. Nageswa...; Caterina Giannini; James M. Olson; László Bognár; Almos Klekner; Karel Zitterbart; Joanna J. Phillips; Reid C. Thompson; Michael K. Cooper; Joshua B. Rubin; Linda M. Liau; Miklós Garami; Peter Hauser; Kay Ka Wai Li; Ho-Keung Ng; Wai Sang Poon; G. Yancey Gillespie; Jennifer A. Chan; Shin Jung; Roger E. McLendon; Eric M. Thompson; David Zagzag; Rajeev Vibhakar; Young Shin Ra; Maria Luisa Garre; Ulrich Schüller; Tomoko Shofuda; Claudia C. Faria; Enrique López-Agu...; Gelareh Zadeh; Chi-Chung Hui; Vijay Ramaswamy; Swneke D. Bailey; Steven J. Jones; Andrew J. Mungall; Richard A. Moore; John A. Calarco; Lincoln D. Stein; Gary D. Bader; Jüri Reimand; Jiannis Ragoussis; William A. Weiss; Marco A. Marra; Hiromichi Suzuki; Michael D. Taylor
• Keywords: GLI2; PTCH1; GNAS complex locus; Loss function

Abstract Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers the developing central nervous system. Here, we use unbiased sequencing transcriptome across large cohort 250 tumors to reveal differences among molecular subtypes disease, demonstrate previously unappreciated importance non-coding RNA transcripts. We identify alterations within cAMP dependent pathway ( GNAS , PRKAR1A ) which converge on GLI2 activity show that 18% have genetic event directly targets abundance and/or stability MYCN. Furthermore, discover an extensive network fusions in focally amplified regions encompassing several loss-of-function tumor suppressor genes PTCH1 SUFU NCOR1 . Molecular convergence subset by nucleotide variants, copy number aberrations, gene highlight key roles specific pathways pathogenesis open up opportunities for therapeutic intervention.