%0 Journal Article
%A Salmerón-Villalobos, Julia
%A Ramis-Zaldivar, Joan Enric
%A Balagué, Olga
%A Verdú-Amorós, Jaime
%A Celis, Verónica
%A Sábado, Constantino
%A Garrido, Marta
%A Mato, Sara
%A Uriz, Javier
%A Ortega, M José
%A Gutierrez-Camino, Angela
%A Sinnett, Daniel
%A Illarregi, Unai
%A Carron, Máxime
%A Regueiro, Alexandra
%A Galera, Ana
%A Gonzalez-Farré, Blanca
%A Campo, Elias
%A Garcia, Noelia
%A Colomer, Dolors
%A Astigarraga, Itziar
%A Andrés, Mara
%A Llavador, Margarita
%A Martin-Guerrero, Idoia
%A Salaverria, Itziar
%T Diverse mutations and structural variations contribute to Notch signaling deregulation in paediatric T-cell lymphoblastic lymphoma.
%D 2022
%U http://hdl.handle.net/10668/22450
%X T-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.
%K Notch
%K T-LBL
%K T-cell lymphoblastic lymphoma
%K molecular genetics
%K paediatric
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