MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism

Pratiti Bandopadhayay, Lori A. Ramkissoon, Payal Jain, Guillaume Bergthold, Jeremiah Wala, Rhamy Zeid, Steven E. Schumacher, Laura Urbanski, Ryan O'Rourke, William J. Gibson, Kristine Pelton, Shakti H. Ramkissoon, Harry J. Han, Yuankun Zhu, Namrata Choudhari, Amanda Silva, Katie Boucher, Rosemary E. Henn, Yun Jee Kang, David Knoff & 42 others Brenton R. Paolella, Adrianne Gladden-Young, Pascale Varlet, Melanie Pages, Peleg M. Horowitz, Alexander Federation, Hayley Malkin, Adam A. Tracy, Sara Seepo, Matthew Ducar, Paul Van Hummelen, Mariarita Santi, Anna Maria Buccoliero, Mirko Scagnet, Daniel C. Bowers, Caterina Giannini, Stephanie Puget, Cynthia Hawkins, Uri Tabori, Almos Klekner, Laszlo Bognar, Peter C. Burger, Charles G Eberhart, Fausto J Rodriguez, D. Ashley Hill, Sabine Mueller, Daphne A. Haas-Kogan, Joanna J. Phillips, Sandro Santagata, Charles D. Stiles, James E. Bradner, Nada Jabado, Alon Goren, Jacques Grill, Azra H. Ligon, Liliana Goumnerova, Angela J. Waanders, Phillip B. Storm, Mark W. Kieran, Keith L. Ligon, Rameen Beroukhim, Adam C. Resnick

Research output: Contribution to journalArticle

Abstract

Angiocentric gliomas are pediatric low-grade gliomas (PLGGs) without known recurrent genetic drivers. We performed genomic analysis of new and published data from 249 PLGGs, including 19 angiocentric gliomas. We identified MYB-QKI fusions as a specific and single candidate driver event in angiocentric gliomas. In vitro and in vivo functional studies show that MYB-QKI rearrangements promote tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression and hemizygous loss of the tumor suppressor QKI. To our knowledge, this represents the first example of a single driver rearrangement simultaneously transforming cells via three genetic and epigenetic mechanisms in a tumor.

Original languageEnglish (US)
Pages (from-to)273-282
Number of pages10
JournalNature Genetics
Volume48
Issue number3
DOIs
StatePublished - Mar 1 2016

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Glioma
Pediatrics
Epigenomics
Neoplasms
Carcinogenesis

ASJC Scopus subject areas

  • Genetics

Cite this

Bandopadhayay, P., Ramkissoon, L. A., Jain, P., Bergthold, G., Wala, J., Zeid, R., ... Resnick, A. C. (2016). MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nature Genetics, 48(3), 273-282. https://doi.org/10.1038/ng.3500

MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. / Bandopadhayay, Pratiti; Ramkissoon, Lori A.; Jain, Payal; Bergthold, Guillaume; Wala, Jeremiah; Zeid, Rhamy; Schumacher, Steven E.; Urbanski, Laura; O'Rourke, Ryan; Gibson, William J.; Pelton, Kristine; Ramkissoon, Shakti H.; Han, Harry J.; Zhu, Yuankun; Choudhari, Namrata; Silva, Amanda; Boucher, Katie; Henn, Rosemary E.; Kang, Yun Jee; Knoff, David; Paolella, Brenton R.; Gladden-Young, Adrianne; Varlet, Pascale; Pages, Melanie; Horowitz, Peleg M.; Federation, Alexander; Malkin, Hayley; Tracy, Adam A.; Seepo, Sara; Ducar, Matthew; Van Hummelen, Paul; Santi, Mariarita; Buccoliero, Anna Maria; Scagnet, Mirko; Bowers, Daniel C.; Giannini, Caterina; Puget, Stephanie; Hawkins, Cynthia; Tabori, Uri; Klekner, Almos; Bognar, Laszlo; Burger, Peter C.; Eberhart, Charles G; Rodriguez, Fausto J; Hill, D. Ashley; Mueller, Sabine; Haas-Kogan, Daphne A.; Phillips, Joanna J.; Santagata, Sandro; Stiles, Charles D.; Bradner, James E.; Jabado, Nada; Goren, Alon; Grill, Jacques; Ligon, Azra H.; Goumnerova, Liliana; Waanders, Angela J.; Storm, Phillip B.; Kieran, Mark W.; Ligon, Keith L.; Beroukhim, Rameen; Resnick, Adam C.

In: Nature Genetics, Vol. 48, No. 3, 01.03.2016, p. 273-282.

Research output: Contribution to journalArticle

Bandopadhayay, P, Ramkissoon, LA, Jain, P, Bergthold, G, Wala, J, Zeid, R, Schumacher, SE, Urbanski, L, O'Rourke, R, Gibson, WJ, Pelton, K, Ramkissoon, SH, Han, HJ, Zhu, Y, Choudhari, N, Silva, A, Boucher, K, Henn, RE, Kang, YJ, Knoff, D, Paolella, BR, Gladden-Young, A, Varlet, P, Pages, M, Horowitz, PM, Federation, A, Malkin, H, Tracy, AA, Seepo, S, Ducar, M, Van Hummelen, P, Santi, M, Buccoliero, AM, Scagnet, M, Bowers, DC, Giannini, C, Puget, S, Hawkins, C, Tabori, U, Klekner, A, Bognar, L, Burger, PC, Eberhart, CG, Rodriguez, FJ, Hill, DA, Mueller, S, Haas-Kogan, DA, Phillips, JJ, Santagata, S, Stiles, CD, Bradner, JE, Jabado, N, Goren, A, Grill, J, Ligon, AH, Goumnerova, L, Waanders, AJ, Storm, PB, Kieran, MW, Ligon, KL, Beroukhim, R & Resnick, AC 2016, 'MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism', Nature Genetics, vol. 48, no. 3, pp. 273-282. https://doi.org/10.1038/ng.3500
Bandopadhayay P, Ramkissoon LA, Jain P, Bergthold G, Wala J, Zeid R et al. MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nature Genetics. 2016 Mar 1;48(3):273-282. https://doi.org/10.1038/ng.3500
Bandopadhayay, Pratiti ; Ramkissoon, Lori A. ; Jain, Payal ; Bergthold, Guillaume ; Wala, Jeremiah ; Zeid, Rhamy ; Schumacher, Steven E. ; Urbanski, Laura ; O'Rourke, Ryan ; Gibson, William J. ; Pelton, Kristine ; Ramkissoon, Shakti H. ; Han, Harry J. ; Zhu, Yuankun ; Choudhari, Namrata ; Silva, Amanda ; Boucher, Katie ; Henn, Rosemary E. ; Kang, Yun Jee ; Knoff, David ; Paolella, Brenton R. ; Gladden-Young, Adrianne ; Varlet, Pascale ; Pages, Melanie ; Horowitz, Peleg M. ; Federation, Alexander ; Malkin, Hayley ; Tracy, Adam A. ; Seepo, Sara ; Ducar, Matthew ; Van Hummelen, Paul ; Santi, Mariarita ; Buccoliero, Anna Maria ; Scagnet, Mirko ; Bowers, Daniel C. ; Giannini, Caterina ; Puget, Stephanie ; Hawkins, Cynthia ; Tabori, Uri ; Klekner, Almos ; Bognar, Laszlo ; Burger, Peter C. ; Eberhart, Charles G ; Rodriguez, Fausto J ; Hill, D. Ashley ; Mueller, Sabine ; Haas-Kogan, Daphne A. ; Phillips, Joanna J. ; Santagata, Sandro ; Stiles, Charles D. ; Bradner, James E. ; Jabado, Nada ; Goren, Alon ; Grill, Jacques ; Ligon, Azra H. ; Goumnerova, Liliana ; Waanders, Angela J. ; Storm, Phillip B. ; Kieran, Mark W. ; Ligon, Keith L. ; Beroukhim, Rameen ; Resnick, Adam C. / MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. In: Nature Genetics. 2016 ; Vol. 48, No. 3. pp. 273-282.
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abstract = "Angiocentric gliomas are pediatric low-grade gliomas (PLGGs) without known recurrent genetic drivers. We performed genomic analysis of new and published data from 249 PLGGs, including 19 angiocentric gliomas. We identified MYB-QKI fusions as a specific and single candidate driver event in angiocentric gliomas. In vitro and in vivo functional studies show that MYB-QKI rearrangements promote tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression and hemizygous loss of the tumor suppressor QKI. To our knowledge, this represents the first example of a single driver rearrangement simultaneously transforming cells via three genetic and epigenetic mechanisms in a tumor.",
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AU - Ramkissoon, Lori A.

AU - Jain, Payal

AU - Bergthold, Guillaume

AU - Wala, Jeremiah

AU - Zeid, Rhamy

AU - Schumacher, Steven E.

AU - Urbanski, Laura

AU - O'Rourke, Ryan

AU - Gibson, William J.

AU - Pelton, Kristine

AU - Ramkissoon, Shakti H.

AU - Han, Harry J.

AU - Zhu, Yuankun

AU - Choudhari, Namrata

AU - Silva, Amanda

AU - Boucher, Katie

AU - Henn, Rosemary E.

AU - Kang, Yun Jee

AU - Knoff, David

AU - Paolella, Brenton R.

AU - Gladden-Young, Adrianne

AU - Varlet, Pascale

AU - Pages, Melanie

AU - Horowitz, Peleg M.

AU - Federation, Alexander

AU - Malkin, Hayley

AU - Tracy, Adam A.

AU - Seepo, Sara

AU - Ducar, Matthew

AU - Van Hummelen, Paul

AU - Santi, Mariarita

AU - Buccoliero, Anna Maria

AU - Scagnet, Mirko

AU - Bowers, Daniel C.

AU - Giannini, Caterina

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AU - Hawkins, Cynthia

AU - Tabori, Uri

AU - Klekner, Almos

AU - Bognar, Laszlo

AU - Burger, Peter C.

AU - Eberhart, Charles G

AU - Rodriguez, Fausto J

AU - Hill, D. Ashley

AU - Mueller, Sabine

AU - Haas-Kogan, Daphne A.

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AU - Grill, Jacques

AU - Ligon, Azra H.

AU - Goumnerova, Liliana

AU - Waanders, Angela J.

AU - Storm, Phillip B.

AU - Kieran, Mark W.

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