Identification of a 3-gene model as a powerful diagnostic tool for the recognition of ALK-negative anaplastic large-cell lymphoma.

TitleIdentification of a 3-gene model as a powerful diagnostic tool for the recognition of ALK-negative anaplastic large-cell lymphoma.
Publication TypeJournal Article
Year of Publication2012
AuthorsAgnelli L, Mereu E, Pellegrino E, Limongi T, Kwee I, Bergaggio E, Ponzoni M, Zamò A, Iqbal J, Piccaluga PPaolo, Neri A, Chan WC, Pileri S, Bertoni F, Inghirami G, Piva R
Corporate AuthorsEuropean T-Cell Lymphoma Study Group
JournalBlood
Volume120
Issue6
Pagination1274-81
Date Published2012 Aug 09
ISSN1528-0020
KeywordsAdult, Anaplastic Lymphoma Kinase, Biomarkers, Tumor, Case-Control Studies, Diagnosis, Differential, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, Neoplasm, Humans, Lymphoma, Large-Cell, Anaplastic, Microarray Analysis, Models, Statistical, Molecular Diagnostic Techniques, Predictive Value of Tests, Prognosis, Receptor Protein-Tyrosine Kinases
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.

DOI10.1182/blood-2012-01-405555
Alternate JournalBlood
PubMed ID22740451
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Giorgio Inghirami, M.D.

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