TREC mediated oncogenesis in human immature T lymphoid malignancies preferentially involves ZFP36L2

Estelle Balducci; Thomas Steimlé; Charlotte Smith; Patrick Villarese; Mélanie Feroul; Dominique Payet-Bornet; Sophie Kaltenbach; Lucile Couronné; Ludovic Lhermitte; Aurore Touzart; Marie-Emilie Dourthe; Mathieu Simonin; André Baruchel; Hervé Dombret; Norbert Ifrah; Nicolas Boissel; Bertrand Nadel; Elizabeth Macintyre; Agata Cieslak; Vahid Asnafi

doi:10.1186/s12943-023-01794-y

TREC mediated oncogenesis in human immature T lymphoid malignancies preferentially involves ZFP36L2

Mol Cancer. 2023 Jul 10;22(1):108. doi: 10.1186/s12943-023-01794-y.

Authors

Estelle Balducci^#^{1

2}, Thomas Steimlé^#^{1

2

3}, Charlotte Smith^{1

2}, Patrick Villarese^{1

2}, Mélanie Feroul^{1

2}, Dominique Payet-Bornet⁴, Sophie Kaltenbach^{1

2}, Lucile Couronné^{1

2}, Ludovic Lhermitte^{1

2}, Aurore Touzart^{1

2}, Marie-Emilie Dourthe^{1

2}, Mathieu Simonin^{1

2}, André Baruchel^{5

6}, Hervé Dombret⁷, Norbert Ifrah⁸, Nicolas Boissel⁷, Bertrand Nadel⁴, Elizabeth Macintyre^{1

2}, Agata Cieslak^{9

10}, Vahid Asnafi^{11

12}

Affiliations

¹ Laboratory of Onco-Hematology, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
² Université Paris Cité, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM), Paris, France.
³ TAGC, UMR 1090, Aix-Marseille University, INSERM, Marseille, France.
⁴ Aix Marseille Université, CNRS, INSERM, CIML, Marseille, France.
⁵ Department of Pediatric Hematology and Immunology, University Hospital Robert Debré, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
⁶ Institut Universitaire d'Hématologie, EA-3518, University Hospital Saint-Louis, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
⁷ Université Paris Diderot, Institut Universitaire d'Hématologie, EA-3518, Assistance Publique-Hôpitaux de Paris, University Hospital Saint-Louis, 75010, Paris, France.
⁸ PRES LUNAM, CHU Angers Service Des Maladies du Sang, INSERM U 892, 49933, Angers, France.
⁹ Laboratory of Onco-Hematology, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. agata.cieslak@aphp.fr.
¹⁰ Université Paris Cité, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM), Paris, France. agata.cieslak@aphp.fr.
¹¹ Laboratory of Onco-Hematology, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. vahid.asnafi@aphp.fr.
¹² Université Paris Cité, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM), Paris, France. vahid.asnafi@aphp.fr.

^# Contributed equally.

Abstract

The reintegration of excised signal joints resulting from human V(D)J recombination was described as a potent source of genomic instability in human lymphoid cancers. However, such molecular events have not been recurrently reported in clinical patient lymphoma/leukemia samples. Using a specifically designed NGS-capture pipeline, we here demonstrated the reintegration of T-cell receptor excision circles (TRECs) in 20/1533 (1.3%) patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). Remarkably, the reintegration of TREC recurrently targeted the tumor suppressor gene, ZFP36L2, in 17/20 samples. Thus, our data identified a new and hardly detectable mechanism of gene deregulation in lymphoid cancers providing new insights in human oncogenesis.

Keywords: Cancer; Oncogenesis; T-cell receptor excision circles (TREC).

Publication types

Letter
Research Support, Non-U.S. Gov't

MeSH terms

Carcinogenesis* / genetics
Cell Transformation, Neoplastic / genetics
Genomic Instability
Hematopoietic Stem Cells
Humans
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
Transcription Factors

Substances

ZFP36L2 protein, human
Transcription Factors