Identification of a three-gene model as a powerful diagnostic tool for the recognition of ALK negative ALCL

Agnelli, L.; Mereu, E.; Pellegrino, E.; Limongi, T.; Kwee, I.; Bergaggio, E.; Ponzoni, M.; Zamò, A.; Iqbal, J.; Piccaluga, P.P.; Neri, A.; Chan, J.C.; Pileri, S.; Bertoni, F.; Inghirami, G.; Piva, R.

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Anaplastic Large Cell Lymphomas (ALCL) are a clinically and biologically heterogeneous disease including the ALK+ and ALK- systemic forms. While ALK+ ALCL 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-NHL) remains controversial. Here, 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 to recognize ALK- ALCL. Application of RT-qPCR in independent data sets from cryopreserved and formalin-fixed paraffin embedded (FFPE) samples validated a three-gene model (TNFRSF8, BATF3, TMOD1) able to successfully separate ALK- ALCL from PTCLNOS, with overall accuracy near 97%. In conclusion, our data justify the possibility to translate RT-qPCR protocols to routine clinical settings as a new approach to objectively dissect T-NHL and to select more appropriate therapeutic protocols.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/429974

Titolo:	Identification of a three-gene model as a powerful diagnostic tool for the recognition of ALK negative ALCL
Autori interni:	ZAMO', Alberto
Data di pubblicazione:	2012
Rivista:	BLOOD
Abstract:	Anaplastic Large Cell Lymphomas (ALCL) are a clinically and biologically heterogeneous disease including the ALK+ and ALK- systemic forms. While ALK+ ALCL 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-NHL) remains controversial. Here, 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 to recognize ALK- ALCL. Application of RT-qPCR in independent data sets from cryopreserved and formalin-fixed paraffin embedded (FFPE) samples validated a three-gene model (TNFRSF8, BATF3, TMOD1) able to successfully separate ALK- ALCL from PTCLNOS, with overall accuracy near 97%. In conclusion, our data justify the possibility to translate RT-qPCR protocols to routine clinical settings as a new approach to objectively dissect T-NHL and to select more appropriate therapeutic protocols.
Handle:	http://hdl.handle.net/11562/429974
Appare nelle tipologie:	01.01 Articolo in Rivista

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