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Br J Haematol. 2019 Apr;185(1):79-88. doi: 10.1111/bjh.15757. Epub 2019 Jan 25.

Expression of ELF1, a lymphoid ETS domain-containing transcription factor, is recurrently lost in classical Hodgkin lymphoma.

Author information

1
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
2
Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
3
Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Science, Poznan, Poland.
4
Department of Tumour Pathology, Greater Poland Cancer Centre, Poznan, Poland.
5
Institute of Human Genetics, Ulm University & Ulm University Medical Centre, Ulm, Germany.
6
Insitut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
7
Institute of Human Genetics, Christian-Albrechts-University Kiel, Kiel, Germany.
8
Department of Pathology, Hematopathology Section and Lymph Node Registry, Christian-Albrechts-University Kiel, Kiel, Germany.
9
Department of Tumour Pathology and Prophylaxis, Poznan University of Medical Sciences & Greater Poland Cancer Centre, Poznan, Poland.

Abstract

Loss of B cell-specific transcription factors (TFs) and the resulting loss of B-cell phenotype of Hodgkin and Reed-Sternberg (HRS) cells is a hallmark of classical Hodgkin lymphoma (cHL). Here we have analysed two members of ETS domain containing TFs, ELF1 and ELF2, regarding (epi)genomic changes as well as gene and protein expression. We observed absence or lower levels of ELF1 protein in HRS cells of 31/35 (89%) cases compared to the bystander cells and significant (P < 0·01) downregulation of the gene on mRNA as well as protein level in cHL compared to non-cHL cell lines. However, no recurrent loss of ELF2 protein was observed. Moreover, ELF1 was targeted by heterozygous deletions combined with hypermethylation of the remaining allele(s) in 4/7 (57%) cell lines. Indeed, DNA hypermethylation (range 95-99%, mean 98%) detected in the vicinity of the ELF1 transcription start site was found in all 7/7 (100%) cHL cell lines. Similarly, 5/18 (28%) analysed primary biopsies carried heterozygous deletions of the gene. We demonstrate that expression of ELF1 is impaired in cHL through genetic and epigenetic alterations, and thus, it may represent an additional member of a TF network whose downregulation contributes to the loss of B-cell phenotype of HRS cells.

KEYWORDS:

ELF1 ; ELF2 ; classical Hodgkin lymphoma; loss of B-cell identity; transcription factors

PMID:
30681722
DOI:
10.1111/bjh.15757

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