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; 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 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

doi:10.1038/ng.3500

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 KnoffBrenton 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 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

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

123 Scopus citations

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 language	English (US)
Pages (from-to)	273-282
Number of pages	10
Journal	Nature Genetics
Volume	48
Issue number	3
DOIs	https://doi.org/10.1038/ng.3500
State	Published - Mar 1 2016

ASJC Scopus subject areas

Genetics

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10.1038/ng.3500

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Bandopadhayay, P., Ramkissoon, L. A., Jain, P., Bergthold, G., Wala, J., Zeid, R., Schumacher, S. E., Urbanski, L., O'Rourke, R., Gibson, W. J., Pelton, K., Ramkissoon, S. H., Han, H. J., Zhu, Y., Choudhari, N., Silva, A., Boucher, K., Henn, R. E., Kang, Y. J., ... 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

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, C, 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

@article{2ada4f5fa7d44bf8a826f4e7bfeffb7c,

title = "MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism",

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.",

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

note = "Funding Information: We thank and acknowledge the Dana-Farber Harvard Cancer Center/Pediatric Low-Grade Astrocytoma Consortium and the Children{\textquoteright}s Brain Tumor Tissue Consortium, including additional participating sites: Ann and Robert Lurie Children{\textquoteright}s Hospital, Seattle Children{\textquoteright}s Hospital and Children{\textquoteright}s Hospital of Pittsburgh for sample contribution, members of the Genomic Platform and Firehose Team at the Broad Institute for assistance with genomic sequencing and analysis, the Neuro-Histology laboratories of Boston Children{\textquoteright}s Hospital and Brigham and Women{\textquoteright}s Hospital, H. Homer (Brigham and Women{\textquoteright}s Hospital) for technical assistance with FISH, and members of the Ligon, Resnick and Beroukhim laboratories for useful discussions. We acknowledge the following funding sources: A Kids{\textquoteright} Brain Tumor Cure Foundation Pediatric Low-Grade Astrocytoma Foundation (P.B., K.L.L., R.B., M.W.K., L.G., C.D.S. and A.C.R.), US National Institutes of Health grant R01NS085336 (A.C.R., A.J.W., P.B.S. and M. Santi), Voices Against Brain Cancer (A.C.R.), the Children{\textquoteright}s Brain Tumor Foundation (A.C.R. and A.J.W.), the Stop and Shop Pediatric Brain Tumor Program (P.B. and M.W.K.), the Path to Cure Foundation (K.L.L.), US National Institutes of Health grant PO1CA142536 (C.D.S., K.L.L. and R.B.), St. Baldrick{\textquoteright}s Foundation (P.B.), the American Brain Tumor Association (L.A.R.), the Team Jack Foundation (P.B., M.W.K., R.B. and L.G.), the Andrysiak Fund for LGG (M.W.K.), a Broad Institute Scientific Projects to Accelerate Research and Collaboration (SPARC) grant (A.G.), the Jared Branfman Sunflowers for Life Fund for Pediatric Brain and Spinal Cancer Research (P.B., R.B. and S. Santagata), the Sontag Foundation (K.L.L. and R.B.), the Nuovo-Soldati Foundation (G.B.), the Philippe Foundation (G.B.), Fondation Etoile de Martin (J.G.), the Damon Runyon-Sohn Pediatric Fellowship Award (A.J.W.), a Hyundai Scholar Grant (A.J.W.), the Bear Necessities Pediatric Cancer Foundation (A.J.W. and A.C.R.), the Rally Foundation for Childhood Cancer Research (A.J.W.), National Institute of Neurological Disorders and Stroke (NINDS) grant K08NS087118 (S.H.R.), the Pediatric Brain Tumor Foundation (R.B. and P.B.), Thea{\textquoteright}s Star of Hope (A.C.R. and A.J.W.), the Hungarian Brain Research Program, grant KTIA_13_NAP-A-V/3, the Janos Bolyai Scholarship of the Hungarian Academy of Sciences (A.K.), NINDS grant 1R01NS091620 (D.A.H.-K.), the Nancy and Stephen Grand Philanthropic Fund (D.A.H.-K.) and the Pediatric Low-Grade Astrocytoma Foundation (D.A.H.-K.). Finally, we thank and acknowledge the many children and families affected by PLGGs for their generous contributions to this research. Funding Information: Low-Grade Astrocytoma Consortium and the Children{\textquoteright}s Brain Tumor Tissue Consortium, including additional participating sites: Ann and Robert Lurie Children{\textquoteright}s Hospital, Seattle Children{\textquoteright}s Hospital and Children{\textquoteright}s Hospital of Pittsburgh for sample contribution, members of the Genomic Platform and Firehose Team at the Broad Institute for assistance with genomic sequencing and analysis, the Neuro-Histology laboratories of Boston Children{\textquoteright}s Hospital and Brigham and Women{\textquoteright}s Hospital, H. Homer (Brigham and Women{\textquoteright}s Hospital) for technical assistance with FISH, and members of the Ligon, Resnick and Beroukhim laboratories for useful discussions. We acknowledge the following funding sources: A Kids{\textquoteright} Brain Tumor Cure Foundation Pediatric Low-Grade Astrocytoma Foundation (P.B., K.L.L., R.B., M.W.K., L.G., C.D.S. and A.C.R.), US National Institutes of Health grant R01NS085336 (A.C.R., A.J.W., P.B.S. and M. Santi), Voices Against Brain Cancer (A.C.R.), the Children{\textquoteright}s Brain Tumor Foundation (A.C.R. and A.J.W.), the Stop and Shop Pediatric Brain Tumor Program (P.B. and M.W.K.), the Path to Cure Foundation (K.L.L.), US National Institutes of Health grant PO1CA142536 (C.D.S., K.L.L. and R.B.), St. Baldrick{\textquoteright}s Foundation (P.B.), the American Brain Tumor Association (L.A.R.), the Team Jack Foundation (P.B., M.W.K., R.B. and L.G.), the Andrysiak Fund for LGG (M.W.K.), a Broad Institute Scientific Projects to Accelerate Research and Collaboration (SPARC) grant (A.G.), the Jared Branfman Sunflowers for Life Fund for Pediatric Brain and Spinal Cancer Research (P.B., R.B. and S. Santagata), the Sontag Foundation (K.L.L. and R.B.), the Nuovo-Soldati Foundation (G.B.), the Philippe Foundation (G.B.), Fondation Etoile de Martin (J.G.), the Damon Runyon-Sohn Pediatric Fellowship Award (A.J.W.), a Hyundai Scholar Grant (A.J.W.), the Bear Necessities Pediatric Cancer Foundation (A.J.W. and A.C.R.), the Rally Foundation for Childhood Cancer Research (A.J.W.), National Institute of Neurological Disorders and Stroke (NINDS) grant K08NS087118 (S.H.R.), the Pediatric Brain Tumor Foundation (R.B. and P.B.), Thea{\textquoteright}s Star of Hope (A.C.R. and A.J.W.), the Hungarian Brain Research Program, grant KTIA-13-NAP-A-V/3, the Janos Bolyai Scholarship of the Hungarian Academy of Sciences (A.K.), NINDS grant 1R01NS091620 (D.A.H.-K.), the Nancy and Stephen Grand Philanthropic Fund (D.A.H.-K.) and the Pediatric Low-Grade Astrocytoma Foundation (D.A.H.-K.). Finally, we thank and acknowledge the many children and families affected by PLGGs for their generous contributions to this research. Publisher Copyright: {\textcopyright} 2016 Nature America, Inc.",

year = "2016",

month = mar,

day = "1",

doi = "10.1038/ng.3500",

language = "English (US)",

volume = "48",

pages = "273--282",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "3",

}

TY - JOUR

T1 - MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism

AU - Bandopadhayay, Pratiti

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

AU - Puget, Stephanie

AU - Hawkins, Cynthia

AU - Tabori, Uri

AU - Klekner, Almos

AU - Bognar, Laszlo

AU - Burger, Peter C.

AU - Eberhart, Charles

AU - Rodriguez, Fausto J.

AU - Hill, D. Ashley

AU - Mueller, Sabine

AU - Haas-Kogan, Daphne A.

AU - Phillips, Joanna J.

AU - Santagata, Sandro

AU - Stiles, Charles D.

AU - Bradner, James E.

AU - Jabado, Nada

AU - Goren, Alon

AU - Grill, Jacques

AU - Ligon, Azra H.

AU - Goumnerova, Liliana

AU - Waanders, Angela J.

AU - Storm, Phillip B.

AU - Kieran, Mark W.

AU - Ligon, Keith L.

AU - Beroukhim, Rameen

AU - Resnick, Adam C.

N1 - Funding Information: We thank and acknowledge the Dana-Farber Harvard Cancer Center/Pediatric Low-Grade Astrocytoma Consortium and the Children’s Brain Tumor Tissue Consortium, including additional participating sites: Ann and Robert Lurie Children’s Hospital, Seattle Children’s Hospital and Children’s Hospital of Pittsburgh for sample contribution, members of the Genomic Platform and Firehose Team at the Broad Institute for assistance with genomic sequencing and analysis, the Neuro-Histology laboratories of Boston Children’s Hospital and Brigham and Women’s Hospital, H. Homer (Brigham and Women’s Hospital) for technical assistance with FISH, and members of the Ligon, Resnick and Beroukhim laboratories for useful discussions. We acknowledge the following funding sources: A Kids’ Brain Tumor Cure Foundation Pediatric Low-Grade Astrocytoma Foundation (P.B., K.L.L., R.B., M.W.K., L.G., C.D.S. and A.C.R.), US National Institutes of Health grant R01NS085336 (A.C.R., A.J.W., P.B.S. and M. Santi), Voices Against Brain Cancer (A.C.R.), the Children’s Brain Tumor Foundation (A.C.R. and A.J.W.), the Stop and Shop Pediatric Brain Tumor Program (P.B. and M.W.K.), the Path to Cure Foundation (K.L.L.), US National Institutes of Health grant PO1CA142536 (C.D.S., K.L.L. and R.B.), St. Baldrick’s Foundation (P.B.), the American Brain Tumor Association (L.A.R.), the Team Jack Foundation (P.B., M.W.K., R.B. and L.G.), the Andrysiak Fund for LGG (M.W.K.), a Broad Institute Scientific Projects to Accelerate Research and Collaboration (SPARC) grant (A.G.), the Jared Branfman Sunflowers for Life Fund for Pediatric Brain and Spinal Cancer Research (P.B., R.B. and S. Santagata), the Sontag Foundation (K.L.L. and R.B.), the Nuovo-Soldati Foundation (G.B.), the Philippe Foundation (G.B.), Fondation Etoile de Martin (J.G.), the Damon Runyon-Sohn Pediatric Fellowship Award (A.J.W.), a Hyundai Scholar Grant (A.J.W.), the Bear Necessities Pediatric Cancer Foundation (A.J.W. and A.C.R.), the Rally Foundation for Childhood Cancer Research (A.J.W.), National Institute of Neurological Disorders and Stroke (NINDS) grant K08NS087118 (S.H.R.), the Pediatric Brain Tumor Foundation (R.B. and P.B.), Thea’s Star of Hope (A.C.R. and A.J.W.), the Hungarian Brain Research Program, grant KTIA_13_NAP-A-V/3, the Janos Bolyai Scholarship of the Hungarian Academy of Sciences (A.K.), NINDS grant 1R01NS091620 (D.A.H.-K.), the Nancy and Stephen Grand Philanthropic Fund (D.A.H.-K.) and the Pediatric Low-Grade Astrocytoma Foundation (D.A.H.-K.). Finally, we thank and acknowledge the many children and families affected by PLGGs for their generous contributions to this research. Funding Information: Low-Grade Astrocytoma Consortium and the Children’s Brain Tumor Tissue Consortium, including additional participating sites: Ann and Robert Lurie Children’s Hospital, Seattle Children’s Hospital and Children’s Hospital of Pittsburgh for sample contribution, members of the Genomic Platform and Firehose Team at the Broad Institute for assistance with genomic sequencing and analysis, the Neuro-Histology laboratories of Boston Children’s Hospital and Brigham and Women’s Hospital, H. Homer (Brigham and Women’s Hospital) for technical assistance with FISH, and members of the Ligon, Resnick and Beroukhim laboratories for useful discussions. We acknowledge the following funding sources: A Kids’ Brain Tumor Cure Foundation Pediatric Low-Grade Astrocytoma Foundation (P.B., K.L.L., R.B., M.W.K., L.G., C.D.S. and A.C.R.), US National Institutes of Health grant R01NS085336 (A.C.R., A.J.W., P.B.S. and M. Santi), Voices Against Brain Cancer (A.C.R.), the Children’s Brain Tumor Foundation (A.C.R. and A.J.W.), the Stop and Shop Pediatric Brain Tumor Program (P.B. and M.W.K.), the Path to Cure Foundation (K.L.L.), US National Institutes of Health grant PO1CA142536 (C.D.S., K.L.L. and R.B.), St. Baldrick’s Foundation (P.B.), the American Brain Tumor Association (L.A.R.), the Team Jack Foundation (P.B., M.W.K., R.B. and L.G.), the Andrysiak Fund for LGG (M.W.K.), a Broad Institute Scientific Projects to Accelerate Research and Collaboration (SPARC) grant (A.G.), the Jared Branfman Sunflowers for Life Fund for Pediatric Brain and Spinal Cancer Research (P.B., R.B. and S. Santagata), the Sontag Foundation (K.L.L. and R.B.), the Nuovo-Soldati Foundation (G.B.), the Philippe Foundation (G.B.), Fondation Etoile de Martin (J.G.), the Damon Runyon-Sohn Pediatric Fellowship Award (A.J.W.), a Hyundai Scholar Grant (A.J.W.), the Bear Necessities Pediatric Cancer Foundation (A.J.W. and A.C.R.), the Rally Foundation for Childhood Cancer Research (A.J.W.), National Institute of Neurological Disorders and Stroke (NINDS) grant K08NS087118 (S.H.R.), the Pediatric Brain Tumor Foundation (R.B. and P.B.), Thea’s Star of Hope (A.C.R. and A.J.W.), the Hungarian Brain Research Program, grant KTIA-13-NAP-A-V/3, the Janos Bolyai Scholarship of the Hungarian Academy of Sciences (A.K.), NINDS grant 1R01NS091620 (D.A.H.-K.), the Nancy and Stephen Grand Philanthropic Fund (D.A.H.-K.) and the Pediatric Low-Grade Astrocytoma Foundation (D.A.H.-K.). Finally, we thank and acknowledge the many children and families affected by PLGGs for their generous contributions to this research. Publisher Copyright: © 2016 Nature America, Inc.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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.

AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84959547851&partnerID=8YFLogxK

U2 - 10.1038/ng.3500

DO - 10.1038/ng.3500

M3 - Article

C2 - 26829751

AN - SCOPUS:84959547851

SN - 1061-4036

VL - 48

SP - 273

EP - 282

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

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

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