Title | Integration of transcriptional and mutational data simplifies the stratification of peripheral T-cell lymphoma. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Maura F, Agnelli L, Leongamornlert D, Bolli N, Chan WC, Dodero A, Carniti C, Heavican TB, Pellegrinelli A, Pruneri G, Butler A, Bhosle SG, Chiappella A, Di Rocco A, Zinzani PLuigi, Zaja F, Piva R, Inghirami G, Wang W, Palomero T, Iqbal J, Neri A, Campbell PJ, Corradini P |
Journal | Am J Hematol |
Volume | 94 |
Issue | 6 |
Pagination | 628-634 |
Date Published | 2019 06 |
ISSN | 1096-8652 |
Keywords | Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Lymphoma, T-Cell, Peripheral, Male, Mutation, Neoplasm Proteins, Transcription, Genetic |
Abstract | The histological diagnosis of peripheral T-cell lymphoma (PTCL) can represent a challenge, particularly in the case of closely related entities such as angioimmunoblastic T-lymphoma (AITL), PTCL-not otherwise specified (PTCL-NOS), and ALK-negative anaplastic large-cell lymphoma (ALCL). Although gene expression profiling and next generations sequencing have been proven to define specific features recurrently associated with distinct entities, genomic-based stratifications have not yet led to definitive diagnostic criteria and/or entered into the routine clinical practice. Herein, to improve the current molecular classification between AITL and PTCL-NOS, we analyzed the transcriptional profiles from 503 PTCLs stratified according to their molecular configuration and integrated them with genomic data of recurrently mutated genes (RHOA , TET2, IDH2 , and DNMT3A) in 53 cases (39 AITLs and 14 PTCL-NOSs) included in the series. Our analysis unraveled that the mutational status of RHOA , TET2, and DNMT3A poorly correlated, individually, with peculiar transcriptional fingerprints. Conversely, in IDH2 samples a strong transcriptional signature was identified that could act as a surrogate for mutational status. The integrated analysis of clinical, mutational, and molecular data led to a simplified 19-gene signature that retains high accuracy in differentiating the main nodal PTCL entities. The expression levels of those genes were confirmed in an independent cohort profiled by RNA-sequencing. |
DOI | 10.1002/ajh.25450 |
Alternate Journal | Am J Hematol |
PubMed ID | 30829413 |
PubMed Central ID | PMC6684242 |
Grant List | P30 CA016672 / CA / NCI NIH HHS / United States R01 CA197945 / CA / NCI NIH HHS / United States #14346 / / Associazione Italiana per la Ricerca sul Cancro / International #16722 / / Associazione Italiana per la Ricerca sul Cancro / International P30 CA008748 / CA / NCI NIH HHS / United States #17658 / / Associazione Italiana per la Ricerca sul Cancro / International #10136 / / Associazione Italiana per la Ricerca sul Cancro / International R01 CA183793 / CA / NCI NIH HHS / United States / / Associazione Italiana Contro le Leucemie - Linfomi e Mieloma / International |
Related Faculty:
Giorgio Inghirami, M.D.