Genomic landscape of T-cell lymphoblastic lymphoma.

Objective: T-cell lymphoblastic lymphoma (T-LBL) is an aggressive neoplasm of precursor T cells, however, detailed genome-wide sequencing of large T-LBL cohorts has not been performed due to its rarity. The purpose of this study was to identify putative driver genes in T-LBL.

Methods: To gain insight into the genetic mechanisms of T-LBL development, we performed whole-exome sequencing on 41 paired tumor-normal DNA samples from patients with T-LBL.

Results: We identified 32 putative driver genes using whole-exome sequencing in 41 T-LBL cases, many of which have not previously been described in T-LBL, such as Janus kinase 3 (), Janus kinase 1 (), Runt-related transcription factor 1 () and Wilms' tumor suppressor gene 1 (). When comparing the genetic alterations of T-LBL to T-cell acute lymphoblastic leukemia (T-ALL), we found that JAK-STAT and RAS pathway mutations were predominantly observed in T-LBL (58.5% and 34.1%, respectively), whereas Notch and cell cycle signaling pathways mutations were more prevalent in T-ALL. Notably, besides notch receptor 1 (), mutational status of plant homeodomain (PHD)-like finger protein 6 () was identified as another independent factor for good prognosis. Of utmost interest is that co-existence of and mutation status might provide an alternative for early therapeutic stratification in T-LBL.

Conclusions: Together, our findings will not only provide new insights into the molecular and genetic mechanisms of T-LBL, but also have tangible implications for clinical practice.