The transcriptional landscape of Shh medulloblastoma
Authors
SKOWRON, P., H. FAROOQ, F. M. G. CAVALLI, A. S. MORRISSY, M. LY, L. D. HENDRIKSE, E. Y. WANG, H. DJAMBAZIAN, H. ZHU, K. L. MUNGALL, Q. M. TRINH, T. N. ZHENG, S. Z. DAI, A. S. G. STUCKLIN, M. C. VLADOIU, V. FONG, B. L. HOLGADO, C. NOR, X. C. WU, D. ABD-RABBO, P. BERUBE, Y. C. WANG, B. LUU, R. A. SUAREZ, A. RASTAN, A. H. GILLMOR, J. J. Y. LEE, X. Y. ZHANG, C. DANIELS, P. DIRKS, D. MALKIN, E. BOUFFET, U. TABORI, J. LOUKIDES, F. P. DOZ, F. BOURDEAUT, O. O. DELATTRE, J. MASLIAH-PLANCHON, O. AYRAULT, S. K. KIM, D. MEYRONET, W. A. GRAJKOWSKA, C. G. CARLOTTI, C. DE TORRES, J. MORA, C. G. EBERHART, E. G. VAN MEIR, T. KUMABE, P. J. FRENCH, J. M. KROS, N. JABADO, B. LACH, I. F. POLLACK, R. L. HAMILTON, A. A. N. RAO, C. GIANNINI, J. M. OLSON, L. BOGNAR, A. KLEKNER, Karel ZITTERBART (203 Czech Republic, belonging to the institution), J. J. PHILLIPS, R. C. THOMPSON, M. K. COOPER, J. B. RUBIN, L. M. LIAU, M. GARAMI, P. HAUSER, K. K. W. LI, H. K. NG, W. S. POON, G. Y. GILLESPIE, J. A. CHAN, S. JUNG, R. E. MCLENDON, E. M. THOMPSON, D. ZAGZAG, R. VIBHAKAR, Y. S. RA, M. L. GARRE, U. SCHULLER, T. SHOFUDA, C. C. FARIA, E. LOPEZ-AGUILAR, G. ZADEH, C. C. HUI, V. RAMASWAMY, S. D. BAILEY, S. J. JONES, A. J. MUNGALL, R. A. MOORE, J. A. CALARCO, L. D. STEIN, G. D. BADER, J. REIMAND, J. RAGOUSSIS, W. A. WEISS, M. A. MARRA, H. SUZUKI (guarantor) and MD TAYLOR
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. Sonic Hedgehog medulloblastoma (Shh-MB) comprises four subtypes each with distinct clinical traits. Here the authors characterize the genome, transcriptome, and methylome of Shh-MB subtypes, revealing a complex fusion landscape and the molecular convergence of MYCN and cAMP signaling pathways.
SKOWRON, P., H. FAROOQ, F. M. G. CAVALLI, A. S. MORRISSY, M. LY, L. D. HENDRIKSE, E. Y. WANG, H. DJAMBAZIAN, H. ZHU, K. L. MUNGALL, Q. M. TRINH, T. N. ZHENG, S. Z. DAI, A. S. G. STUCKLIN, M. C. VLADOIU, V. FONG, B. L. HOLGADO, C. NOR, X. C. WU, D. ABD-RABBO, P. BERUBE, Y. C. WANG, B. LUU, R. A. SUAREZ, A. RASTAN, A. H. GILLMOR, J. J. Y. LEE, X. Y. ZHANG, C. DANIELS, P. DIRKS, D. MALKIN, E. BOUFFET, U. TABORI, J. LOUKIDES, F. P. DOZ, F. BOURDEAUT, O. O. DELATTRE, J. MASLIAH-PLANCHON, O. AYRAULT, S. K. KIM, D. MEYRONET, W. A. GRAJKOWSKA, C. G. CARLOTTI, C. DE TORRES, J. MORA, C. G. EBERHART, E. G. VAN MEIR, T. KUMABE, P. J. FRENCH, J. M. KROS, N. JABADO, B. LACH, I. F. POLLACK, R. L. HAMILTON, A. A. N. RAO, C. GIANNINI, J. M. OLSON, L. BOGNAR, A. KLEKNER, Karel ZITTERBART, J. J. PHILLIPS, R. C. THOMPSON, M. K. COOPER, J. B. RUBIN, L. M. LIAU, M. GARAMI, P. HAUSER, K. K. W. LI, H. K. NG, W. S. POON, G. Y. GILLESPIE, J. A. CHAN, S. JUNG, R. E. MCLENDON, E. M. THOMPSON, D. ZAGZAG, R. VIBHAKAR, Y. S. RA, M. L. GARRE, U. SCHULLER, T. SHOFUDA, C. C. FARIA, E. LOPEZ-AGUILAR, G. ZADEH, C. C. HUI, V. RAMASWAMY, S. D. BAILEY, S. J. JONES, A. J. MUNGALL, R. A. MOORE, J. A. CALARCO, L. D. STEIN, G. D. BADER, J. REIMAND, J. RAGOUSSIS, W. A. WEISS, M. A. MARRA, H. SUZUKI and MD TAYLOR. The transcriptional landscape of Shh medulloblastoma. Nature Communications. London: Nature Publishing Group, 2021, vol. 12, No 1, p. 1-17. ISSN 2041-1723. Available from: https://dx.doi.org/10.1038/s41467-021-21883-0.
@article{1786879, author = {Skowron, P. and Farooq, H. and Cavalli, F. M. G. and Morrissy, A. S. and Ly, M. and Hendrikse, L. D. and Wang, E. Y. and Djambazian, H. and Zhu, H. and Mungall, K. L. and Trinh, Q. M. and Zheng, T. N. and Dai, S. Z. and Stucklin, A. S. G. and Vladoiu, M. C. and Fong, V. and Holgado, B. L. and Nor, C. and Wu, X. C. and AbdandRabbo, D. and Berube, P. and Wang, Y. C. and Luu, B. and Suarez, R. A. and Rastan, A. and Gillmor, A. H. and Lee, J. J. Y. and Zhang, X. Y. and Daniels, C. and Dirks, P. and Malkin, D. and Bouffet, E. and Tabori, U. and Loukides, J. and Doz, F. P. and Bourdeaut, F. and Delattre, O. O. and MasliahandPlanchon, J. and Ayrault, O. and Kim, S. K. and Meyronet, D. and Grajkowska, W. A. and Carlotti, C. G. and de Torres, C. and Mora, J. and Eberhart, C. G. and Van Meir, E. G. and Kumabe, T. and French, P. J. and Kros, J. M. and Jabado, N. and Lach, B. and Pollack, I. F. and Hamilton, R. L. and Rao, A. A. N. and Giannini, C. and Olson, J. M. and Bognar, L. and Klekner, A. and Zitterbart, Karel and Phillips, J. J. and Thompson, R. C. and Cooper, M. K. and Rubin, J. B. and Liau, L. M. and Garami, M. and Hauser, P. and Li, K. K. W. and Ng, H. K. and Poon, W. S. and Gillespie, G. Y. and Chan, J. A. and Jung, S. and McLendon, R. E. and Thompson, E. M. and Zagzag, D. and Vibhakar, R. and Ra, Y. S. and Garre, M. L. and Schuller, U. and Shofuda, T. and Faria, C. C. and LopezandAguilar, E. and Zadeh, G. and Hui, C. C. and Ramaswamy, V. and Bailey, S. D. and Jones, S. J. and Mungall, A. J. and Moore, R. A. and Calarco, J. A. and Stein, L. D. and Bader, G. D. and Reimand, J. and Ragoussis, J. and Weiss, W. A. and Marra, M. A. and Suzuki, H. and Taylor, MD}, article_location = {London}, article_number = {1}, doi = {http://dx.doi.org/10.1038/s41467-021-21883-0}, keywords = {Shh medulloblastoma; transcriptional landscape}, language = {eng}, issn = {2041-1723}, journal = {Nature Communications}, title = {The transcriptional landscape of Shh medulloblastoma}, url = {https://www.nature.com/articles/s41467-021-21883-0}, volume = {12}, year = {2021} }
TY - JOUR ID - 1786879 AU - Skowron, P. - Farooq, H. - Cavalli, F. M. G. - Morrissy, A. S. - Ly, M. - Hendrikse, L. D. - Wang, E. Y. - Djambazian, H. - Zhu, H. - Mungall, K. L. - Trinh, Q. M. - Zheng, T. N. - Dai, S. Z. - Stucklin, A. S. G. - Vladoiu, M. C. - Fong, V. - Holgado, B. L. - Nor, C. - Wu, X. C. - Abd-Rabbo, D. - Berube, P. - Wang, Y. C. - Luu, B. - Suarez, R. A. - Rastan, A. - Gillmor, A. H. - Lee, J. J. Y. - Zhang, X. Y. - Daniels, C. - Dirks, P. - Malkin, D. - Bouffet, E. - Tabori, U. - Loukides, J. - Doz, F. P. - Bourdeaut, F. - Delattre, O. O. - Masliah-Planchon, J. - Ayrault, O. - Kim, S. K. - Meyronet, D. - Grajkowska, W. A. - Carlotti, C. G. - de Torres, C. - Mora, J. - Eberhart, C. G. - Van Meir, E. G. - Kumabe, T. - French, P. J. - Kros, J. M. - Jabado, N. - Lach, B. - Pollack, I. F. - Hamilton, R. L. - Rao, A. A. N. - Giannini, C. - Olson, J. M. - Bognar, L. - Klekner, A. - Zitterbart, Karel - Phillips, J. J. - Thompson, R. C. - Cooper, M. K. - Rubin, J. B. - Liau, L. M. - Garami, M. - Hauser, P. - Li, K. K. W. - Ng, H. K. - Poon, W. S. - Gillespie, G. Y. - Chan, J. A. - Jung, S. - McLendon, R. E. - Thompson, E. M. - Zagzag, D. - Vibhakar, R. - Ra, Y. S. - Garre, M. L. - Schuller, U. - Shofuda, T. - Faria, C. C. - Lopez-Aguilar, E. - Zadeh, G. - Hui, C. C. - Ramaswamy, V. - Bailey, S. D. - Jones, S. J. - Mungall, A. J. - Moore, R. A. - Calarco, J. A. - Stein, L. D. - Bader, G. D. - Reimand, J. - Ragoussis, J. - Weiss, W. A. - Marra, M. A. - Suzuki, H. - Taylor, MD PY - 2021 TI - The transcriptional landscape of Shh medulloblastoma JF - Nature Communications VL - 12 IS - 1 SP - 1-17 EP - 1-17 PB - Nature Publishing Group SN - 20411723 KW - Shh medulloblastoma KW - transcriptional landscape UR - https://www.nature.com/articles/s41467-021-21883-0 N2 - 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. Sonic Hedgehog medulloblastoma (Shh-MB) comprises four subtypes each with distinct clinical traits. Here the authors characterize the genome, transcriptome, and methylome of Shh-MB subtypes, revealing a complex fusion landscape and the molecular convergence of MYCN and cAMP signaling pathways. ER -
SKOWRON, P., H. FAROOQ, F. M. G. CAVALLI, A. S. MORRISSY, M. LY, L. D. HENDRIKSE, E. Y. WANG, H. DJAMBAZIAN, H. ZHU, K. L. MUNGALL, Q. M. TRINH, T. N. ZHENG, S. Z. DAI, A. S. G. STUCKLIN, M. C. VLADOIU, V. FONG, B. L. HOLGADO, C. NOR, X. C. WU, D. ABD-RABBO, P. BERUBE, Y. C. WANG, B. LUU, R. A. SUAREZ, A. RASTAN, A. H. GILLMOR, J. J. Y. LEE, X. Y. ZHANG, C. DANIELS, P. DIRKS, D. MALKIN, E. BOUFFET, U. TABORI, J. LOUKIDES, F. P. DOZ, F. BOURDEAUT, O. O. DELATTRE, J. MASLIAH-PLANCHON, O. AYRAULT, S. K. KIM, D. MEYRONET, W. A. GRAJKOWSKA, C. G. CARLOTTI, C. DE TORRES, J. MORA, C. G. EBERHART, E. G. VAN MEIR, T. KUMABE, P. J. FRENCH, J. M. KROS, N. JABADO, B. LACH, I. F. POLLACK, R. L. HAMILTON, A. A. N. RAO, C. GIANNINI, J. M. OLSON, L. BOGNAR, A. KLEKNER, Karel ZITTERBART, J. J. PHILLIPS, R. C. THOMPSON, M. K. COOPER, J. B. RUBIN, L. M. LIAU, M. GARAMI, P. HAUSER, K. K. W. LI, H. K. NG, W. S. POON, G. Y. GILLESPIE, J. A. CHAN, S. JUNG, R. E. MCLENDON, E. M. THOMPSON, D. ZAGZAG, R. VIBHAKAR, Y. S. RA, M. L. GARRE, U. SCHULLER, T. SHOFUDA, C. C. FARIA, E. LOPEZ-AGUILAR, G. ZADEH, C. C. HUI, V. RAMASWAMY, S. D. BAILEY, S. J. JONES, A. J. MUNGALL, R. A. MOORE, J. A. CALARCO, L. D. STEIN, G. D. BADER, J. REIMAND, J. RAGOUSSIS, W. A. WEISS, M. A. MARRA, H. SUZUKI and MD TAYLOR. The transcriptional landscape of Shh medulloblastoma. \textit{Nature Communications}. London: Nature Publishing Group, 2021, vol.~12, No~1, p.~1-17. ISSN~2041-1723. Available from: https://dx.doi.org/10.1038/s41467-021-21883-0.