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Loss of function mutations of BCOR in classical Hodgkin lymphoma

Giefing, Maciej (author)
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.
Gearhart, Micah D. (author)
Univ Minnesota, Masonic Canc Ctr, Dept Genet Cell Biol & Dev, Minneapolis, MN USA.;Univ Minnesota, Dev Biol Ctr, Minneapolis, MN USA.
Schneider, Markus (author)
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.
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Overbeck, Birte (author)
Christian Albrechts Univ Kiel, Inst Human Genet, Kiel, Germany.;Univ Hosp Schleswig Holstein, Kiel, Germany.
Klapper, Wolfram (author)
Christian Albrechts Univ Kiel, Dept Pathol, Haematopathol Sect, Kiel, Germany.;Christian Albrechts Univ Kiel, Lymph Node Registry, Kiel, Germany.
Hartmann, Sylvia (author)
Goethe Univ Frankfurt, Dr Senckenberg Inst Pathol, Med Sch, Reference & Consultant Ctr Lymph Node & Lymphoma, Frankfurt, Germany.
Ustaszewski, Adam (author)
Polish Acad Sci, Inst Human Genet, Strzeszynska 32, PL-60479 Poznan, Poland.
Weniger, Marc A. (author)
Univ Duisburg Essen, Med Fac, Inst Cell Biol Canc Res, Essen, Germany.;Deutsch Konsortium Translat Krebsforsch DKTK, Heidelberg, Germany.
Wiehle, Laura (author)
Univ Ulm, Inst Human Genet, Ulm, Germany.;Univ Ulm, Med Ctr, Ulm, Germany.
Hansmann, Martin-Leo (author)
Goethe Univ Frankfurt, Dr Senckenberg Inst Pathol, Med Sch, Reference & Consultant Ctr Lymph Node & Lymphoma, Frankfurt, Germany.
Melnick, Ari (author)
Weill Cornell Med, Dept Med, Div Hematol Oncol, New York, NY USA.
Beguelin, Wendy (author)
Weill Cornell Med, Dept Med, Div Hematol Oncol, New York, NY USA.
Sundström, Christer (author)
Uppsala universitet,Klinisk och experimentell patologi
Küppers, Ralf (author)
Univ Duisburg Essen, Med Fac, Inst Cell Biol Canc Res, Essen, Germany.;Deutsch Konsortium Translat Krebsforsch DKTK, Heidelberg, Germany.
Bardwell, Vivian J. (author)
Univ Minnesota, Masonic Canc Ctr, Dept Genet Cell Biol & Dev, Minneapolis, MN USA.;Univ Minnesota, Dev Biol Ctr, Minneapolis, MN USA.
Siebert, Reiner (author)
Christian Albrechts Univ Kiel, Inst Human Genet, Kiel, Germany.;Univ Hosp Schleswig Holstein, Kiel, Germany.;Univ Ulm, Inst Human Genet, Ulm, Germany.;Univ Ulm, Med Ctr, Ulm, Germany.
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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. Univ Minnesota, Masonic Canc Ctr, Dept Genet Cell Biol & Dev, Minneapolis, MN USA.;Univ Minnesota, Dev Biol Ctr, Minneapolis, MN USA. (creator_code:org_t)
2021-12-27
2022
English.
In: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 63:5, s. 1080-1090
Related links:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

Classical Hodgkin lymphoma
microdissection
BCOR
Polycomb
PRC1

Publication and Content Type

ref (subject category)
art (subject category)

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