The histological diagnosis of peripheral T-cell lymphoma (PTCL) can represent a challenge, particularly in the case of closely related entities like 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 (RHOAG17V , TET2, IDH2R172 , DNMT3A) in 53 cases (39 AITLs and 14 PTCL-NOSs) included in the series. Our analysis unraveled that the mutational status of RHOAG17V , TET2 and DNMT3A poorly correlated, individually, with peculiar transcriptional fingerprints. Conversely, in IDH2R172 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.

Integration of Transcriptional and Mutational Data Simplifies the Stratification of Peripheral T-Cell Lymphoma / F. Maura, L. Agnelli, D. Leongamornlert, N. Bolli, J. Chan, A. Dodero, C. Carniti, T.B. Heavican, A. Pellegrinelli, G. Pruneri, A. Butler, S.G. Bhosle, A. Chiappella, A. Di Rocco, P.L. Zinzani, F. Zaja, R. Piva, G. Inghirami, W. Wang, T. Palomero, J. Iqbal, A. Neri, P.J. Campbell, P. Corradini. - In: AMERICAN JOURNAL OF HEMATOLOGY. - ISSN 0361-8609. - 94:6(2019), pp. 628-634. [10.1002/ajh.25450]

Integration of Transcriptional and Mutational Data Simplifies the Stratification of Peripheral T-Cell Lymphoma

F. Maura;L. Agnelli;N. Bolli;A. Pellegrinelli;G. Pruneri;A. Neri;P. Corradini
2019

Abstract

The histological diagnosis of peripheral T-cell lymphoma (PTCL) can represent a challenge, particularly in the case of closely related entities like 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 (RHOAG17V , TET2, IDH2R172 , DNMT3A) in 53 cases (39 AITLs and 14 PTCL-NOSs) included in the series. Our analysis unraveled that the mutational status of RHOAG17V , TET2 and DNMT3A poorly correlated, individually, with peculiar transcriptional fingerprints. Conversely, in IDH2R172 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.
Settore MED/15 - Malattie del Sangue
2019
Article (author)
File in questo prodotto:
File Dimensione Formato  
Maura_Am J Hematol_2019.pdf

Open Access dal 22/05/2020

Tipologia: Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione 3 MB
Formato Adobe PDF
3 MB Adobe PDF Visualizza/Apri
Maura_et_al-2019-American_Journal_of_Hematology.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.99 MB
Formato Adobe PDF
1.99 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/630313
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 14
social impact