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

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...

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Bibliographic Details
Published in:Molecular cancer 2023-07, Vol.22 (1), p.108-108, Article 108
Main Authors: Balducci, Estelle, Steimlé, Thomas, Smith, Charlotte, Villarese, Patrick, Feroul, Mélanie, Payet-Bornet, Dominique, Kaltenbach, Sophie, Couronné, Lucile, Lhermitte, Ludovic, Touzart, Aurore, Dourthe, Marie-Emilie, Simonin, Mathieu, Baruchel, André, Dombret, Hervé, Ifrah, Norbert, Boissel, Nicolas, Nadel, Bertrand, Macintyre, Elizabeth, Cieslak, Agata, Asnafi, Vahid
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Antigens
B cells
Biochemistry, Molecular Biology
Cancer
Carcinogenesis
Carcinogenesis - genetics
Cell Transformation, Neoplastic - genetics
Correspondence
Genes
Genomes
Genomic Instability
Genomics
Hematology
Hematopoietic Stem Cells
Human health and pathology
Humans
Leukemia
Life Sciences
Lymphocytes T
Lymphoma
Malignancy
Mitochondrial DNA
Non-Hodgkin's lymphomas
Oncogenesis
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics
Proteins
T cell receptors
T cells
T-cell receptor excision circles (TREC)
Transcription Factors
Tumor suppressor genes
Tumorigenesis
Tumors
V(D)J recombination
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Summary: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.
ISSN:1476-4598
1476-4598
DOI:10.1186/s12943-023-01794-y