Molecular characterization of T-cell lymphoblastic lymphoma in children and adolescents reveals candidates of clinical relevance

T-cell lymphoblastic lymphoma (T-LBL) is a heterogeneous malignancy of lymphoblasts committed to T-cell lineage. Dismal outcomes (15-30%) in case of T-LBL relapses warrants for risk-based treatment to be established in future. This is a first comprehensive, systematic, integrated genome-wide analysis including relapse cases aimed towards identifying molecular markers of prognostic relevance for T-LBL. Whole exome sequencing (WES) was performed on "limited cohort" of 16 T-LBL cases which included 6 relapse cases. Validation of WES data was performed on a large cohort (n=131) referred as "extended cohort". In order to identify copy number alterations and determine the epigenetic changes SNP arrays and methylation arrays were also performed respectively on the “limited cohort”. Activated NOTCH/PI3K-AKT signaling axis and alterations in cell cycle regulators constitutes the core oncogenic program for T-LBL. KMT2D was identified as a prognostic molecular marker, KMT2Dmut and/or PTENmut associated with poor prognosis.