Salmerón-Villalobos, JuliaRamis-Zaldivar, Joan EnricBalagué, OlgaVerdú-Amorós, JaimeCelis, VerónicaSábado, ConstantinoGarrido, MartaMato, SaraUriz, JavierOrtega, M JoséGutierrez-Camino, AngelaSinnett, DanielIllarregi, UnaiCarron, MáximeRegueiro, AlexandraGalera, AnaGonzalez-Farré, BlancaCampo, EliasGarcia, NoeliaColomer, DolorsAstigarraga, ItziarAndrés, MaraLlavador, MargaritaMartin-Guerrero, IdoiaSalaverria, Itziar2023-05-032023-05-032022-08-24http://hdl.handle.net/10668/22450T-cell lymphoblastic lymphoma (T-LBL) is an aggressive neoplasm closely related to T-cell acute lymphoblastic leukaemia (T-ALL). Despite their similarities, and contrary to T-ALL, studies on paediatric T-LBL are scarce and, therefore, its molecular landscape has not yet been fully elucidated. Thus, the aims of this study were to characterize the genetic and molecular heterogeneity of paediatric T-LBL and to evaluate novel molecular markers differentiating this entity from T-ALL. Thirty-three paediatric T-LBL patients were analyzed using an integrated approach, including targeted next-generation sequencing, RNA-sequencing transcriptome analysis and copy-number arrays. Copy number and mutational analyses allowed the detection of recurrent homozygous deletions of 9p/CDKN2A (78%), trisomy 20 (19%) and gains of 17q24-q25 (16%), as well as frequent mutations of NOTCH1 (62%), followed by the BCL11B (23%), WT1 (19%) and FBXW7, PHF6 and RPL10 genes (15%, respectively). This genetic profile did not differ from that described in T-ALL in terms of mutation incidence and global genomic complexity level, but unveiled virtually exclusive 17q25 gains and trisomy 20 in T-LBL. Additionally, we identified novel gene fusions in paediatric T-LBL, including NOTCH1-IKZF2, RNGTT-SNAP91 and DDX3X-MLLT10, the last being the only one previously described in T-ALL. Moreover, clinical correlations highlighted the presence of Notch pathway alterations as a factor related to favourable outcome. In summary, the genomic landscape of paediatric T-LBL is similar to that observed in T-ALL, and Notch signaling pathway deregulation remains the cornerstone in its pathogenesis, including not only mutations but fusion genes targeting NOTCH1.enNotchT-LBLT-cell lymphoblastic lymphomamolecular geneticspaediatricChildChromosomes, Human, Pair 20F-Box-WD Repeat-Containing Protein 7HumansLymphoma, T-CellMosaicismMutationPrecursor T-Cell Lymphoblastic Leukemia-LymphomaRNAReceptor, Notch1Signal TransductionT-LymphocytesTranscription FactorsTrisomyTumor Suppressor Proteinsresearch article36000950open access10.1002/pbc.299261545-5017https://doi.org/10.22541/au.165165320.05970525/v1