title: Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma.
abstract: Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P = .01). High expression of cytotoxic gene-signature within the TBX21 subgroup also showed poor clinical outcome (P = .05). In AITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P = .004).
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE;
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.forename: George
authors.initials: G
authors.lastname: Wright
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Lynette
authors.initials: L
authors.lastname: Smith
authors.forename: Shuangping
authors.initials: S
authors.lastname: Guo
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Wilcox
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.forename: Soon Thye
authors.initials: ST
authors.lastname: Lim
authors.forename: Soon Yong
authors.initials: SY
authors.lastname: Tan
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Antonio
authors.initials: A
authors.lastname: Martinez
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: James R
authors.initials: JR
authors.lastname: Cook
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tubbs
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Eva
authors.initials: E
authors.lastname: Geissinger
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.forename: Wing Y
authors.initials: WY
authors.lastname: Au
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
authors.forename: Francoise
authors.initials: F
authors.lastname: Berger
authors.forename: Laurence
authors.initials: L
authors.lastname: de Leval
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: James
authors.initials: J
authors.lastname: Armitage
authors.forename: Julie
authors.initials: J
authors.lastname: Vose
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016411:Lymphoma, T-Cell, Peripheral / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor