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Loss of function mutations of BCOR in classical Hodgkin lymphoma
Polish Acad Sci, Inst Human Genet, Strzeszynska 32, PL-60479 Poznan, Poland.;Christian Albrechts Univ Kiel, Inst Human Genet, Kiel, Germany.;Univ Hosp Schleswig Holstein, Kiel, Germany..ORCID iD: 0000-0002-4760-8246
Univ Minnesota, Masonic Canc Ctr, Dept Genet Cell Biol & Dev, Minneapolis, MN USA.;Univ Minnesota, Dev Biol Ctr, Minneapolis, MN USA..
Univ Duisburg Essen, Med Fac, Inst Cell Biol Canc Res, Essen, Germany.;Deutsch Konsortium Translat Krebsforsch DKTK, Heidelberg, Germany.;Univ Childrens Hosp Essen, Dept Pediat Hematol & Oncol, Essen, Germany..
Christian Albrechts Univ Kiel, Inst Human Genet, Kiel, Germany.;Univ Hosp Schleswig Holstein, Kiel, Germany..
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2022 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 63, no 5, p. 1080-1090Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Informa UK Limited Taylor & Francis, 2022. Vol. 63, no 5, p. 1080-1090
Keywords [en]
Classical Hodgkin lymphoma, microdissection, BCOR, Polycomb, PRC1
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-479422DOI: 10.1080/10428194.2021.2015587ISI: 000734839100001PubMedID: 34957890OAI: oai:DiVA.org:uu-479422DiVA, id: diva2:1679078
Funder
German Research Foundation (DFG)EU, Horizon 2020, 952304Available from: 2022-06-30 Created: 2022-06-30 Last updated: 2024-12-03Bibliographically approved

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Sundström, Christer

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