T-cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) share common morphological and immunophenotypic features and are treated with similar therapeutic approaches. Nonetheless, they show distinct clinical presentations, suggesting that they may represent two different biological entities. To investigate the genetic characteristics of T-LBL and T-ALL, we used genomic and transcriptional profiling approaches. Genome-wide gene expression profiling, performed on 20 T-LBL and 10 T-ALL diagnostic specimens, revealed that the two malignancies shared a large fraction of their transcriptional profile while a subset of genes appeared to be differentially expressed in T-LBL versus T-ALL. This signature included genes involved in chemotactic responses and angiogenesis, which may play a role in tumor cell localization. Genome-wide copy number alteration analysis was performed on a subset of the samples analyzed by gene expression profiling and detected 41 recurrently altered genetic loci. Although most aberrations were found in both entities, several were selectively identified in T-LBL or T-ALL. In addition, NOTCH1 mutational status was found to correlate with a subset of genetic aberrations. Taken together, these results suggest that T-LBL and T-ALL are indeed two distinct diseases with unique transcriptional and genetic characteristics.

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http://dx.doi.org/10.1002/gcc.20924DOI Listing

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