Genetic drivers of oncogenic pathways in molecular subgroups of peripheral T-cell lymphoma.

Détails

ID Serval
serval:BIB_61A356E54251
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genetic drivers of oncogenic pathways in molecular subgroups of peripheral T-cell lymphoma.
Périodique
Blood
Auteur(s)
Heavican T.B., Bouska A., Yu J., Lone W., Amador C., Gong Q., Zhang W., Li Y., Dave B.J., Nairismägi M.L., Greiner T.C., Vose J., Weisenburger D.D., Lachel C., Wang C., Fu K., Stevens J.M., Lim S.T., Ong C.K., Gascoyne R.D., Missiaglia E., Lemonnier F., Haioun C., Hartmann S., Pedersen M.B., Laginestra M.A., Wilcox R.A., Teh B.T., Yoshida N., Ohshima K., Seto M., Rosenwald A., Ott G., Campo E., Rimsza L.M., Jaffe E.S., Braziel R.M., d'Amore F., Inghirami G., Bertoni F., de Leval L., Gaulard P., Staudt L.M., McKeithan T.W., Pileri S., Chan W.C., Iqbal J.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Statut éditorial
Publié
Date de publication
11/04/2019
Peer-reviewed
Oui
Volume
133
Numéro
15
Pages
1664-1676
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Peripheral T-cell lymphoma (PTCL) is a group of complex clinicopathological entities, often associated with an aggressive clinical course. Angioimmunoblastic T-cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS) are the 2 most frequent categories, accounting for >50% of PTCLs. Gene expression profiling (GEP) defined molecular signatures for AITL and delineated biological and prognostic subgroups within PTCL-NOS (PTCL-GATA3 and PTCL-TBX21). Genomic copy number (CN) analysis and targeted sequencing of these molecular subgroups revealed unique CN abnormalities (CNAs) and oncogenic pathways, indicating distinct oncogenic evolution. PTCL-GATA3 exhibited greater genomic complexity that was characterized by frequent loss or mutation of tumor suppressor genes targeting the CDKN2A/B-TP53 axis and PTEN-PI3K pathways. Co-occurring gains/amplifications of STAT3 and MYC occurred in PTCL-GATA3. Several CNAs, in particular loss of CDKN2A, exhibited prognostic significance in PTCL-NOS as a single entity and in the PTCL-GATA3 subgroup. The PTCL-TBX21 subgroup had fewer CNAs, primarily targeting cytotoxic effector genes, and was enriched in mutations of genes regulating DNA methylation. CNAs affecting metabolic processes regulating RNA/protein degradation and T-cell receptor signaling were common in both subgroups. AITL showed lower genomic complexity compared with other PTCL entities, with frequent co-occurring gains of chromosome 5 (chr5) and chr21 that were significantly associated with IDH2 <sup>R172</sup> mutation. CN losses were enriched in genes regulating PI3K-AKT-mTOR signaling in cases without IDH2 mutation. Overall, we demonstrated that novel GEP-defined PTCL subgroups likely evolve by distinct genetic pathways and provided biological rationale for therapies that may be investigated in future clinical trials.
Pubmed
Web of science
Création de la notice
25/02/2019 13:11
Dernière modification de la notice
20/08/2019 15:18
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