Abstract SY38-02: Molecular oncogenesis of human T-cell lymphoma: Common features with myeloid malignancies

Abstract

Abstract T-cell lymphomas are a heterogeneous group of diseases associated with poor outcome whose molecular bases are ill characterized. Prompted by the effect of Tet2 inactivation in lymphoid differentiation and the co occurrence of lymphoma in patients with myeloid neoplasm with TET2 mutations, we uncovered TET2 mutations in 2% of B-cell lymphoma and 11% of T-cell lymphoma samples. The highest frequency of TET2 mutation in T-cell lymphoma was observed in the ImmunoAngioblastic (AITL) (10/30: 30%) and the Peripheral T-cell lymphoma, Not otherwise specified (PTCL, NOS) (6/30:20%) subtypes. Cellular analyses showed that TET2 mutations in AITL patients may also be observed in CD34+ hematopoietic progenitors able to differentiate along the myeloid lineages, indicating that TET2 mutations may have occurred in an immature progenitor able to differentiate along both lymphoid and myeloid lineages. Current data indicate that TET2 participate to the control of DNA methylation, through the oxydation of methylcytosine, and therefore the epigenetic control of transcription. Further candidate gene sequencing showed DNMT3A mutations in 11% of T-cell lymphoma samples. In our series, DNMT3A mutations were significantly associated with the presence of TET2 mutations since 8 of the 11 DNMT3A mutated patients also carried a TET2 mutation. In some DNMT3A-mutated-patients, those mutations could be observed during an MDS phase, which had preceded the lymphoma phase. Our data point at transformation pathways common to T-cell lymphoma and myeloid neoplasms. They suggest deregulation of DNA methylation and and provide a further basis for the molecular classification of T-cell lymphomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY38-02. doi:1538-7445.AM2012-SY38-02