Genetic Landscape and Classification of Peripheral T Cell Lymphomas

Peripheral T cell lymphomas (PTCLs) are markedly heterogeneous at the clinical, pathological, and molecular levels. This review will discuss genetic findings in PTCL with special emphasis on how they impact lymphoma classification.

Sequencing studies have identified recurrent genetic alterations in nearly every PTCL subtype. In anaplastic large cell lymphoma, these studies have revealed novel chromosomal rearrangements and mutations that have prognostic significance and may suggest new therapeutic approaches. Angioimmunoblastic T cell lymphoma has been found to have mutations overlapping some cases of PTCL, not otherwise specified with a T follicular helper cell phenotype. Across various subtypes, recurrent mutations and structural alterations affecting genes involved in epigenetic regulation, T cell receptor signaling, and immune response may represent targets for precision therapy approaches. New genetic findings are refining the classification of PTCLs and are beginning to be used clinically for diagnosis, risk stratification, and individualized therapy.