title: Identification of a 3-gene model as a powerful diagnostic tool for the recognition of ALK-negative anaplastic large-cell lymphoma.
abstract: Anaplastic large-cell lymphomas (ALCLs) are a group of clinically and biologically heterogeneous diseases including the ALK(+) and ALK(-) systemic forms. Whereas ALK(+) ALCLs are molecularly characterized and can be readily diagnosed, specific immunophenotypic or genetic features to define ALK(-) ALCL are missing, and their distinction from other T-cell non-Hodgkin lymphomas (T-NHLs) remains controversial. In the present study, we undertook a transcriptional profiling meta-analysis of 309 cases, including ALCL and other primary T-NHL samples. Pathway discovery and prediction analyses defined a minimum set of genes capable of recognizing ALK(-) ALCL. Application of quantitative RT-PCR in independent datasets from cryopreserved and formalin-fixed paraffin-embedded samples validated a 3-gene model (TNFRSF8, BATF3, and TMOD1) able to successfully separate ALK(-) ALCL from peripheral T-cell lymphoma not otherwise specified, with overall accuracy near 97%. In conclusion, our data justify the possibility of translating quantitative RT-PCR protocols to routine clinical settings as a new approach to objectively dissect T-NHL and to select more appropriate therapeutic protocols.
authors: Department of Clinical Sciences and Community Health, University of Milano, Hematology 1, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors: Luca
authors: L
authors: Agnelli
authors: Elisabetta
authors: E
authors: Mereu
authors: Elisa
authors: E
authors: Pellegrino
authors: Tania
authors: T
authors: Limongi
authors: Ivo
authors: I
authors: Kwee
authors: Elisa
authors: E
authors: Bergaggio
authors: Maurilio
authors: M
authors: Ponzoni
authors: Alberto
authors: A
authors: Zamò
authors: Javeed
authors: J
authors: Iqbal
authors: Pier Paolo
authors: PP
authors: Piccaluga
authors: Antonino
authors: A
authors: Neri
authors: Wing C
authors: WC
authors: Chan
authors: Stefano
authors: S
authors: Pileri
authors: Francesco
authors: F
authors: Bertoni
authors: Giorgio
authors: G
authors: Inghirami
authors: Roberto
authors: R
authors: Piva
mesh_terms: D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000502:physiology; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000175:diagnosis* / Q000235:genetics*; D046228:Microarray Analysis; D015233:Models, Statistical; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases