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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2004

The mutator pathway is a feature of immunodeficiency-related lymphomas.

Alex Duval
  • Fonction : Auteur
Martine Raphael
  • Fonction : Auteur
Caroline Brennetot
  • Fonction : Auteur
Helene Poirel
  • Fonction : Auteur
Olivier Buhard
  • Fonction : Auteur
Alban Aubry
  • Fonction : Auteur
Antoine Martin
  • Fonction : Auteur
Amor Krimi
  • Fonction : Auteur
Veronique Leblond
  • Fonction : Auteur
Jean Gabarre
  • Fonction : Auteur
Frederic Davi
  • Fonction : Auteur
Frederic Charlotte
  • Fonction : Auteur
Francoise Berger
  • Fonction : Auteur
Gianluca Gaidano
  • Fonction : Auteur
Daniela Capello
  • Fonction : Auteur
Danielle Canioni
  • Fonction : Auteur
Philippe Gaulard
  • Fonction : Auteur
Marie Helene Delfau
  • Fonction : Auteur
Sophie Ferlicot
  • Fonction : Auteur
Virginie Eclache
Sophie Prevot
  • Fonction : Auteur
Catherine Guettier
Pascale Cornillet Lefevre
  • Fonction : Auteur
Francoise Adotti
  • Fonction : Auteur
Richard Hamelin
  • Fonction : Auteur

Résumé

The mutator phenotype caused by defects in the mismatch repair system is observed in a subset of solid neoplasms characterized by widespread microsatellite instability-high (MSI-H). It is known to be very rare in non-Hodgkin lymphomas (NHL), whereas mutator NHL is the most frequent tumor subtype in mismatch repair-deficient mice. By screening a series of 603 human NHL with specific markers of the mutator phenotype, we found here 12 MSI-H cases (12/603, 2%). Of interest, we demonstrated that this phenotype was specifically associated with immunodeficiency-related lymphomas (ID-RL), because it was observed in both posttransplant lymphoproliferative disorders (9/111, 8.1%) and HIV infection-related lymphomas (3/128, 2.3%) but not in a large series of NHL arising in the general population (0/364) (P < 0.0001). The MSI pathway is known to lead to the production of hundreds of abnormal protein neoantigens that are generated in MSI-H neoplasms by frameshift mutations of a number of genes containing coding microsatellite sequences. As expected, MSI-H ID-RL were found to harbor such genetic alterations in 12 target genes with a putative role in lymphomagenesis. The observation that the MSI-H phenotype was restricted to HIV infection-related lymphomas and posttransplant lymphoproliferative disorders suggests the existence of the highly immunogenic mutator pathway as a novel oncogenic process in lymphomagenesis whose role is favored when host immunosurveillance is reduced. Because MSI-H-positive cases were found to be either Epstein-Barr virus-positive or -negative, the mutator pathway should act synergistically or not with this other oncogenic factor, playing an important role in ID-RL.

Domaines

Immunologie

Dates et versions

hal-00023370 , version 1 (25-04-2006)

Identifiants

Citer

Alex Duval, Martine Raphael, Caroline Brennetot, Helene Poirel, Olivier Buhard, et al.. The mutator pathway is a feature of immunodeficiency-related lymphomas.. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101 (14), pp.5002-7. ⟨10.1073/pnas.0400945101⟩. ⟨hal-00023370⟩
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