Development of a customized gene panel for prognostic and diagnostic evaluation of peripheral nodal T-cell lymphoma

• Grant number: 22/12233-9
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2023
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Juliana Pereira
• Grantee: Juliana Pereira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Cadiele Oliana Reichert ; Carlos Murga-Zamalloa ; Débora Levy ; Francisco Vega ; Hebert Fabricio Culler ; Jessica Ruivo Maximino ; Luís Alberto de Pádua Covas Lage ; Mario L Marques-Piubelli ; Ryan Wilcox ; Sergio Paulo Bydlowski

Abstract

Peripheral T-cell lymphomas (PTCL) constitute a heterogeneous group of rare malignancies, derived from the monoclonal proliferation of post-thymic and activated T-cells and natural-killer (NK) lymphocytes. PTCL encompasses heterogeneous disorders, with distinct clinical, histopathological, immunophenotypic and molecular-genetic characteristics. To date, 29 specific subtypes of PTCL have been described. According to the 2016-World Health Organization (WHO) Classification, these lymphoma subtypes are grouped according to their clinical presentation in predominantly nodal, extranodal, primary cutaneous and disseminated or leukemic. The nodal subtype is composed by peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), angioimmunoblastic T-cell lymphoma (AITL), nodal peripheral T-cell lymphomas with T-helper follicular phenotype (nPTCL-THf), anaplastic large-cell lymphoma (ALCL) anaplastic lymphoma kinase-1 (ALK-1) positive and systemic anaplastic large-cell lymphoma ALK-1 negative (ALK1-negative ALCL). Distinguishing between these nodal PTCL subtypes is quite difficult in clinical practice due to the overlap of clinical, histological and genetic-molecular aspects. In addition, the risk scores used for PTCL have low accuracy in predicting their prognosis. In this sense, there is an unmet medical need in relation to the rapid and accurate establishment of a precise diagnosis of the different subtypes of nodal PTCL. Technologies applied for this purpose should be accessible, cost-effective and universally available. Therefore, performing whole exome sequencing (WES) from patients with nodal PTCL, we aimed to standardize a minimal gene panel capable of assisting in its differential diagnosis and for predicting its prognosis. (AU)