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

被引:92
作者
Agnelli, Luca [2 ,3 ]
Mereu, Elisabetta [1 ]
Pellegrino, Elisa [1 ]
Limongi, Tania [1 ]
Kwee, Ivo [4 ,5 ]
Bergaggio, Elisa [1 ]
Ponzoni, Maurilio [6 ,7 ]
Zamo, Alberto [8 ]
Iqbal, Javeed [9 ]
Piccaluga, Pier Paolo [10 ]
Neri, Antonino [2 ,3 ]
Chan, Wing C. [9 ]
Pileri, Stefano [10 ]
Bertoni, Francesco [4 ,11 ]
Inghirami, Giorgio [1 ,12 ,13 ]
Piva, Roberto [1 ,12 ,13 ]
机构
[1] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Ctr Expt Res & Med Studies, I-10126 Turin, Italy
[2] Osped Maggiore Policlin, Fdn Ist Ricovero & Cura Carattere Sci Ca Granda, Milan, Italy
[3] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy
[4] Oncol Res Inst, Lymphoma & Genom Res Program, Bellinzona, Switzerland
[5] Dalle Molle Inst Artificial Intelligence, Manno, Switzerland
[6] Ist Sci San Raffaele, Pathol Unit, I-20132 Milan, Italy
[7] Ist Sci San Raffaele, Lymphoid Malignancies Unit, I-20132 Milan, Italy
[8] Univ Verona, Dept Pathol, I-37100 Verona, Italy
[9] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA
[10] Univ Bologna, Inst Hematol & Med Oncol, S Orsola Malpighi Hosp, Bologna, Italy
[11] Oncol Inst So Switzerland, Lymphoma Unit, Bellinzona, Switzerland
[12] NYU, Sch Med, Ctr Canc, New York, NY USA
[13] NYU, Sch Med, Dept Pathol, New York, NY USA
关键词
PERIPHERAL T-CELL; GENE-EXPRESSION ANALYSIS; KINASE; CLASSIFICATION; ABERRATIONS; PROFILE;
D O I
10.1182/blood-2012-01-405555
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (Blood. 2012;120(6):1274-1281)
引用
收藏
页码:1274 / 1281
页数:8
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