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 G17V , TET2, IDH2 R172 , and DNMT3A) in 53 cases (39 AITLs and 14 PTCL-NOSs) included in the series. Our analysis unraveled that the mutational status of RHOA G17V , TET2, and DNMT3A poorly correlated, individually, with peculiar transcriptional fingerprints. Conversely, in IDH2 R172 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

Chiappella, Annalisa;Piva, Roberto;Inghirami, Giorgio;Corradini, Paolo
2019

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 G17V , TET2, IDH2 R172 , and DNMT3A) in 53 cases (39 AITLs and 14 PTCL-NOSs) included in the series. Our analysis unraveled that the mutational status of RHOA G17V , TET2, and DNMT3A poorly correlated, individually, with peculiar transcriptional fingerprints. Conversely, in IDH2 R172 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.
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634
http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1096-8652
Hematology, peripheral T‐cell lymphoma, gene expression profiling, molecular classification, IDH2
Maura, Francesco; Agnelli, Luca; Leongamornlert, Daniel; Bolli, Niccolò; Chan, Wing C.; Dodero, Anna; Carniti, Cristiana; Heavican, Tayla B.; Pellegrinelli, Alessio; Pruneri, Giancarlo; Butler, Adam; Bhosle, Shriram G.; Chiappella, Annalisa; Di Rocco, Alice; Zinzani, Pier Luigi; Zaja, Francesco; Piva, Roberto; Inghirami, Giorgio; Wang, Wenyi; Palomero, Teresa; Iqbal, Javeed; Neri, Antonino; Campbell, Peter J.; Corradini, Paolo
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1696663
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