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

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

keywords

  • T-cell receptor excision circles TREC
  • Oncogenesis
  • Cancer

document type

ART

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.

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