Loss of function mutations of BCOR in classical Hodgkin lymphoma. Issue 5 (16th April 2022)

• Record Type: Journal Article
• Authors: Giefing, Maciej; Gearhart, Micah D.; Schneider, Markus; Overbeck, Birte; Klapper, Wolfram; Hartmann, Sylvia; Ustaszewski, Adam; Weniger, Marc A.; Wiehle, Laura; Hansmann, Martin-Leo; Melnick, Ari; Béguelin, Wendy; Sundström, Christer; Küppers, Ralf; Bardwell, Vivian J.; Siebert, Reiner
• Is Part Of: Leukemia & lymphoma. Volume 63:Issue 5(2022)
• Page Start: 1080
• Page End: 1090
• Publication Date: 2022-04-16
• Subjects: Classical Hodgkin lymphoma -- microdissection -- BCOR -- Polycomb -- PRC1; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2021.2015587
• Languages: English
• ISSNs: 1042-8194

Abstract

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.