IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v471y2011i7337d10.1038_nature09730.html
   My bibliography  Save this article

Inactivating mutations of acetyltransferase genes in B-cell lymphoma

Author

Listed:
  • Laura Pasqualucci

    (Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University
    Columbia University)

  • David Dominguez-Sola

    (Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University)

  • Annalisa Chiarenza

    (Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University)

  • Giulia Fabbri

    (Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University)

  • Adina Grunn

    (Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University)

  • Vladimir Trifonov

    (Columbia University)

  • Lawryn H. Kasper

    (St Jude Children’s Research Hospital)

  • Stephanie Lerach

    (St Jude Children’s Research Hospital)

  • Hongyan Tang

    (Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University)

  • Jing Ma

    (The Hartwell Center for Bioinformatics and Biotechnology, St Jude Children’s Research Hospital)

  • Davide Rossi

    (Amedeo Avogadro University of Eastern Piedmont)

  • Amy Chadburn

    (Northwestern University, Feinberg School of Medicine)

  • Vundavalli V. Murty

    (Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University
    Columbia University)

  • Charles G. Mullighan

    (St Jude Children’s Research Hospital)

  • Gianluca Gaidano

    (Amedeo Avogadro University of Eastern Piedmont)

  • Raul Rabadan

    (Columbia University)

  • Paul K. Brindle

    (St Jude Children’s Research Hospital)

  • Riccardo Dalla-Favera

    (Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University
    Columbia University
    Columbia University)

Abstract

B-cell non-Hodgkin’s lymphoma comprises biologically and clinically distinct diseases the pathogenesis of which is associated with genetic lesions affecting oncogenes and tumour-suppressor genes. We report here that the two most common types—follicular lymphoma and diffuse large B-cell lymphoma—harbour frequent structural alterations inactivating CREBBP and, more rarely, EP300, two highly related histone and non-histone acetyltransferases (HATs) that act as transcriptional co-activators in multiple signalling pathways. Overall, about 39% of diffuse large B-cell lymphoma and 41% of follicular lymphoma cases display genomic deletions and/or somatic mutations that remove or inactivate the HAT coding domain of these two genes. These lesions usually affect one allele, suggesting that reduction in HAT dosage is important for lymphomagenesis. We demonstrate specific defects in acetylation-mediated inactivation of the BCL6 oncoprotein and activation of the p53 tumour suppressor. These results identify CREBBP/EP300 mutations as a major pathogenetic mechanism shared by common forms of B-cell non-Hodgkin’s lymphoma, with direct implications for the use of drugs targeting acetylation/deacetylation mechanisms.

Suggested Citation

  • Laura Pasqualucci & David Dominguez-Sola & Annalisa Chiarenza & Giulia Fabbri & Adina Grunn & Vladimir Trifonov & Lawryn H. Kasper & Stephanie Lerach & Hongyan Tang & Jing Ma & Davide Rossi & Amy Chad, 2011. "Inactivating mutations of acetyltransferase genes in B-cell lymphoma," Nature, Nature, vol. 471(7337), pages 189-195, March.
  • Handle: RePEc:nat:nature:v:471:y:2011:i:7337:d:10.1038_nature09730
    DOI: 10.1038/nature09730
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature09730
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/nature09730?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Guozhong Jiang & Zhizhong Wang & Zhenguo Cheng & Weiwei Wang & Shuangshuang Lu & Zifang Zhang & Chinedu A. Anene & Faraz Khan & Yue Chen & Emma Bailey & Huisha Xu & Yunshu Dong & Peinan Chen & Zhongxi, 2024. "The integrated molecular and histological analysis defines subtypes of esophageal squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Longxia Xu & Hongwen Xuan & Wei He & Liang Zhang & Mengying Huang & Kuai Li & Hong Wen & Han Xu & Xiaobing Shi, 2023. "TAZ2 truncation confers overactivation of p300 and cellular vulnerability to HDAC inhibition," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Misuzu Habazaki & Shinsuke Mizumoto & Hidetoshi Kajino & Tomoya Kujirai & Hitoshi Kurumizaka & Shigehiro A. Kawashima & Kenzo Yamatsugu & Motomu Kanai, 2023. "A chemical catalyst enabling histone acylation with endogenous acyl-CoA," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Josefine Radke & Naveed Ishaque & Randi Koll & Zuguang Gu & Elisa Schumann & Lina Sieverling & Sebastian Uhrig & Daniel Hübschmann & Umut H. Toprak & Cristina López & Xavier Pastor Hostench & Simone B, 2022. "The genomic and transcriptional landscape of primary central nervous system lymphoma," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    5. Laura Selicato & Flavia Esposito & Grazia Gargano & Maria Carmela Vegliante & Giuseppina Opinto & Gian Maria Zaccaria & Sabino Ciavarella & Attilio Guarini & Nicoletta Del Buono, 2021. "A New Ensemble Method for Detecting Anomalies in Gene Expression Matrices," Mathematics, MDPI, vol. 9(8), pages 1-26, April.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:471:y:2011:i:7337:d:10.1038_nature09730. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.