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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
Nature genetics | 2016

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.

Pubmed ID: 26829751 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA188228
  • Agency: NINDS NIH HHS, United States
    Id: 1R01NS091620
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL007627
  • Agency: NCI NIH HHS, United States
    Id: P01 CA142536
  • Agency: NHGRI NIH HHS, United States
    Id: T32 HG002295
  • Agency: NCI NIH HHS, United States
    Id: P01CA142536
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007753
  • Agency: NINDS NIH HHS, United States
    Id: K08 NS087118
  • Agency: NINDS NIH HHS, United States
    Id: R01NS085336
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS085336
  • Agency: NINDS NIH HHS, United States
    Id: K08NS087118
  • Agency: NCI NIH HHS, United States
    Id: F30 CA192725
  • Agency: NCI NIH HHS, United States
    Id: F32 CA180653

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