Research ExplorerPublicationsThe transcriptional landscape of Shh medulloblastoma

The transcriptional landscape of Shh medulloblastoma

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The transcriptional landscape of Shh medulloblastoma. / Skowron, Patryk; Farooq, Hamza; Cavalli, Florence M G; Morrissy, A Sorana; Ly, Michelle; Hendrikse, Liam D; Wang, Evan Y; Djambazian, Haig; Zhu, Helen; Mungall, Karen L; Trinh, Quang M; Zheng, Tina; Dai, Shizhong; Stucklin, Ana S Guerreiro; Vladoiu, Maria C; Fong, Vernon; Holgado, Borja L; Nor, Carolina; Wu, Xiaochong; Abd-Rabbo, Diala; Bérubé, Pierre; Wang, Yu Chang; Luu, Betty; Suarez, Raul A; Rastan, Avesta; Gillmor, Aaron H; Lee, John J Y; Zhang, Xiao Yun; Daniels, Craig; Dirks, Peter; Malkin, David; Bouffet, Eric; Tabori, Uri; Loukides, James; Doz, François P; Bourdeaut, Franck; Delattre, Olivier O; Masliah-Planchon, Julien; Ayrault, Olivier; 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; Kros, Johan M; Jabado, Nada; Lach, Boleslaw; Pollack, Ian F; Hamilton, Ronald L; Rao, Amulya A Nageswara; Giannini, Caterina; Olson, James M; Bognár, László; Klekner, Almos; Zitterbart, Karel; Phillips, Joanna J; Thompson, Reid C; Cooper, Michael K; Rubin, Joshua B; Liau, Linda M; Garami, Miklós; 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, Ulrich; Shofuda, Tomoko; Faria, Claudia C; López-Aguilar, Enrique; Zadeh, Gelareh; Hui, Chi-Chung; Ramaswamy, Vijay; Bailey, Swneke D; Jones, Steven J; Mungall, Andrew J; Moore, Richard A; Calarco, John A; Stein, Lincoln D; Bader, Gary D; Reimand, Jüri; Ragoussis, Jiannis; Weiss, William A; Marra, Marco A; Suzuki, Hiromichi; Taylor, Michael D.

In: NAT COMMUN, Vol. 12, No. 1, 19.03.2021, p. 1749.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Skowron, P, Farooq, H, Cavalli, FMG, Morrissy, AS, Ly, M, Hendrikse, LD, Wang, EY, Djambazian, H, Zhu, H, Mungall, KL, Trinh, QM, Zheng, T, Dai, S, Stucklin, ASG, Vladoiu, MC, Fong, V, Holgado, BL, Nor, C, Wu, X, Abd-Rabbo, D, Bérubé, P, Wang, YC, Luu, B, Suarez, RA, Rastan, A, Gillmor, AH, Lee, JJY, Zhang, XY, Daniels, C, Dirks, P, Malkin, D, Bouffet, E, Tabori, U, Loukides, J, Doz, FP, Bourdeaut, F, Delattre, OO, Masliah-Planchon, J, Ayrault, O, Kim, S-K, Meyronet, D, Grajkowska, WA, Carlotti, CG, de Torres, C, Mora, J, Eberhart, CG, Van Meir, EG, Kumabe, T, French, PJ, Kros, JM, Jabado, N, Lach, B, Pollack, IF, Hamilton, RL, Rao, AAN, Giannini, C, Olson, JM, Bognár, L, Klekner, A, Zitterbart, K, Phillips, JJ, Thompson, RC, Cooper, MK, Rubin, JB, Liau, LM, Garami, M, Hauser, P, Li, KKW, Ng, H-K, Poon, WS, Yancey Gillespie, G, Chan, JA, Jung, S, McLendon, RE, Thompson, EM, Zagzag, D, Vibhakar, R, Ra, YS, Garre, ML, Schüller, U, Shofuda, T, Faria, CC, López-Aguilar, E, Zadeh, G, Hui, C-C, Ramaswamy, V, Bailey, SD, Jones, SJ, Mungall, AJ, Moore, RA, Calarco, JA, Stein, LD, Bader, GD, Reimand, J, Ragoussis, J, Weiss, WA, Marra, MA, Suzuki, H & Taylor, MD 2021, 'The transcriptional landscape of Shh medulloblastoma', NAT COMMUN, vol. 12, no. 1, pp. 1749. https://doi.org/10.1038/s41467-021-21883-0

APA

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., Dai, S., Stucklin, A. S. G., Vladoiu, M. C., Fong, V., Holgado, B. L., Nor, C., Wu, X., ... Taylor, M. D. (2021). The transcriptional landscape of Shh medulloblastoma. NAT COMMUN, 12(1), 1749. https://doi.org/10.1038/s41467-021-21883-0

Vancouver

Skowron P, Farooq H, Cavalli FMG, Morrissy AS, Ly M, Hendrikse LD et al. The transcriptional landscape of Shh medulloblastoma. NAT COMMUN. 2021 Mar 19;12(1):1749. https://doi.org/10.1038/s41467-021-21883-0

Bibtex

@article{b2c9d529da71435597cc6701c15a134f,
title = "The transcriptional landscape of Shh medulloblastoma",
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.",
keywords = "Adolescent, Adult, Cerebellar Neoplasms/genetics, Child, Child, Preschool, Female, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Genetic Variation, Hedgehog Proteins/genetics, Humans, Infant, Male, Medulloblastoma/genetics, Middle Aged, Signal Transduction/genetics, Transcriptome, Young Adult",
author = "Patryk Skowron and Hamza Farooq and Cavalli, {Florence M G} and Morrissy, {A Sorana} and Michelle Ly and Hendrikse, {Liam D} and Wang, {Evan Y} and Haig Djambazian and Helen Zhu and Mungall, {Karen L} and Trinh, {Quang M} and Tina Zheng and Shizhong Dai and Stucklin, {Ana S Guerreiro} and Vladoiu, {Maria C} and Vernon Fong and Holgado, {Borja L} and Carolina Nor and Xiaochong Wu and Diala Abd-Rabbo and Pierre B{\'e}rub{\'e} and Wang, {Yu Chang} and Betty Luu and Suarez, {Raul A} and Avesta Rastan and Gillmor, {Aaron H} and Lee, {John J Y} and Zhang, {Xiao Yun} and Craig Daniels and Peter Dirks and David Malkin and Eric Bouffet and Uri Tabori and James Loukides and Doz, {Fran{\c c}ois P} and Franck Bourdeaut and Delattre, {Olivier O} and Julien Masliah-Planchon and Olivier Ayrault and Seung-Ki Kim and David Meyronet and Grajkowska, {Wieslawa A} and Carlotti, {Carlos G} and {de Torres}, Carmen and Jaume Mora and Eberhart, {Charles G} and {Van Meir}, {Erwin G} and Toshihiro Kumabe and French, {Pim J} and Kros, {Johan M} and Nada Jabado and Boleslaw Lach and Pollack, {Ian F} and Hamilton, {Ronald L} and Rao, {Amulya A Nageswara} and Caterina Giannini and Olson, {James M} and L{\'a}szl{\'o} Bogn{\'a}r and Almos Klekner and Karel Zitterbart and Phillips, {Joanna J} and Thompson, {Reid C} and Cooper, {Michael K} and Rubin, {Joshua B} and Liau, {Linda M} and Mikl{\'o}s Garami and Peter Hauser and Li, {Kay Ka Wai} and Ho-Keung Ng and Poon, {Wai Sang} and {Yancey Gillespie}, G and Chan, {Jennifer A} and Shin Jung and McLendon, {Roger E} and Thompson, {Eric M} and David Zagzag and Rajeev Vibhakar and Ra, {Young Shin} and Garre, {Maria Luisa} and Ulrich Sch{\"u}ller and Tomoko Shofuda and Faria, {Claudia C} and Enrique L{\'o}pez-Aguilar and Gelareh Zadeh and Chi-Chung Hui and Vijay Ramaswamy and Bailey, {Swneke D} and Jones, {Steven J} and Mungall, {Andrew J} and Moore, {Richard A} and Calarco, {John A} and Stein, {Lincoln D} and Bader, {Gary D} and J{\"u}ri Reimand and Jiannis Ragoussis and Weiss, {William A} and Marra, {Marco A} and Hiromichi Suzuki and Taylor, {Michael D}",
year = "2021",
month = mar,
day = "19",
doi = "10.1038/s41467-021-21883-0",
language = "English",
volume = "12",
pages = "1749",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - The transcriptional landscape of Shh medulloblastoma

AU - Skowron, Patryk

AU - Farooq, Hamza

AU - Cavalli, Florence M G

AU - Morrissy, A Sorana

AU - Ly, Michelle

AU - Hendrikse, Liam D

AU - Wang, Evan Y

AU - Djambazian, Haig

AU - Zhu, Helen

AU - Mungall, Karen L

AU - Trinh, Quang M

AU - Zheng, Tina

AU - Dai, Shizhong

AU - Stucklin, Ana S Guerreiro

AU - Vladoiu, Maria C

AU - Fong, Vernon

AU - Holgado, Borja L

AU - Nor, Carolina

AU - Wu, Xiaochong

AU - Abd-Rabbo, Diala

AU - Bérubé, Pierre

AU - Wang, Yu Chang

AU - Luu, Betty

AU - Suarez, Raul A

AU - Rastan, Avesta

AU - Gillmor, Aaron H

AU - Lee, John J Y

AU - Zhang, Xiao Yun

AU - Daniels, Craig

AU - Dirks, Peter

AU - Malkin, David

AU - Bouffet, Eric

AU - Tabori, Uri

AU - Loukides, James

AU - Doz, François P

AU - Bourdeaut, Franck

AU - Delattre, Olivier O

AU - Masliah-Planchon, Julien

AU - Ayrault, Olivier

AU - Kim, Seung-Ki

AU - Meyronet, David

AU - Grajkowska, Wieslawa A

AU - Carlotti, Carlos G

AU - de Torres, Carmen

AU - Mora, Jaume

AU - Eberhart, Charles G

AU - Van Meir, Erwin G

AU - Kumabe, Toshihiro

AU - French, Pim J

AU - Kros, Johan M

AU - Jabado, Nada

AU - Lach, Boleslaw

AU - Pollack, Ian F

AU - Hamilton, Ronald L

AU - Rao, Amulya A Nageswara

AU - Giannini, Caterina

AU - Olson, James M

AU - Bognár, László

AU - Klekner, Almos

AU - Zitterbart, Karel

AU - Phillips, Joanna J

AU - Thompson, Reid C

AU - Cooper, Michael K

AU - Rubin, Joshua B

AU - Liau, Linda M

AU - Garami, Miklós

AU - Hauser, Peter

AU - Li, Kay Ka Wai

AU - Ng, Ho-Keung

AU - Poon, Wai Sang

AU - Yancey Gillespie, G

AU - Chan, Jennifer A

AU - Jung, Shin

AU - McLendon, Roger E

AU - Thompson, Eric M

AU - Zagzag, David

AU - Vibhakar, Rajeev

AU - Ra, Young Shin

AU - Garre, Maria Luisa

AU - Schüller, Ulrich

AU - Shofuda, Tomoko

AU - Faria, Claudia C

AU - López-Aguilar, Enrique

AU - Zadeh, Gelareh

AU - Hui, Chi-Chung

AU - Ramaswamy, Vijay

AU - Bailey, Swneke D

AU - Jones, Steven J

AU - Mungall, Andrew J

AU - Moore, Richard A

AU - Calarco, John A

AU - Stein, Lincoln D

AU - Bader, Gary D

AU - Reimand, Jüri

AU - Ragoussis, Jiannis

AU - Weiss, William A

AU - Marra, Marco A

AU - Suzuki, Hiromichi

AU - Taylor, Michael D

PY - 2021/3/19

Y1 - 2021/3/19

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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Cerebellar Neoplasms/genetics

KW - Child

KW - Child, Preschool

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Gene Regulatory Networks

KW - Genetic Variation

KW - Hedgehog Proteins/genetics

KW - Humans

KW - Infant

KW - Male

KW - Medulloblastoma/genetics

KW - Middle Aged

KW - Signal Transduction/genetics

KW - Transcriptome

KW - Young Adult

U2 - 10.1038/s41467-021-21883-0

DO - 10.1038/s41467-021-21883-0

M3 - SCORING: Journal article

C2 - 33741928

VL - 12

SP - 1749

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -