Loss of function mutations of BCOR in classical Hodgkin lymphoma

Maciej Giefing, Micah D. Gearhart, Markus Schneider, Birte Overbeck, Wolfram Klapper, Sylvia Hartmann, Adam Ustaszewski, Marc A. Weniger, Laura Wiehle, Martin Leo Hansmann, Ari Melnick, Wendy Béguelin, Christer Sundström, Ralf Küppers, Vivian J. Bardwell, Reiner Siebert

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

BCOR is a component of a variant Polycomb repressive complex 1 (PRC1.1). PRC1 and PRC2 complexes together constitute a major gene regulatory system critical for appropriate cellular differentiation. The gene is upregulated in germinal center (GC) B cells and mutated in a number of hematologic malignancies. We report BCOR inactivating alterations in 4/7 classic Hodgkin lymphoma (cHL) cell lines, subclonal somatic mutations in Hodgkin and Reed–Sternberg (HRS) cells of 4/10 cHL cases, and deletions in HRS cells of 7/17 primary cHL cases. In mice, conditional loss of Bcor driven by AID-Cre in GC B cells resulted in gene expression changes of 46 genes (>2-fold) including upregulated Lef1 that encodes a transcription factor responsible for establishing T-cell identity and Il9r (interleukin-9 receptor), an important member of the cytokine network in cHL. Our findings suggest a role for BCOR loss in cHL pathogenesis and GC-B cell homeostasis.

Original languageEnglish (US)
Pages (from-to)1080-1090
Number of pages11
JournalLeukemia and Lymphoma
Volume63
Issue number5
DOIs
StatePublished - 2022

Bibliographical note

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© 2021 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • BCOR
  • Classical Hodgkin lymphoma
  • PRC1
  • Polycomb
  • microdissection

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