RT Journal Article T1 Chronic lymphocytic leukemia patients with IGH translocations are characterized by a distinct genetic landscape with prognostic implications A1 Pérez‐Carretero, Claudia A1 Hernández Sánchez, María A1 González, Teresa A1 Quijada‐Álamo, Miguel A1 Martín‐Izquierdo, Marta A1 Vidal, María‐Jesús A1 García de Coca, Alfonso A1 Hernández Rivas, José Ángel A1 Aguilar, Carlos A1 Vargas‐Pabón, Manuel A1 Alonso, Sara A1 Sierra, Magdalena A1 Rubio‐Martínez, Araceli A1 Dávila, Julio A1 Díaz‐Valdés, José R. A1 Queizán, José‐Antonio A1 Benito, Rocío A1 Rodríguez‐Vicente, Ana E. A1 Hernández‐Rivas, Jesús‐María AB Chromosome 14q32 rearrangements/translocations involving the immunoglobulinheavy chain (IGH) are rarely detected in chronic lymphocytic leukemia (CLL). Theprognostic significance of the IGH translocation is controversial and its mutational profile remains unknown. Here, we present for the first time a comprehensive next-generation sequencing (NGS) analysis of 46 CLL patients with IGH rearrangement(IGHR-CLLs) and we demonstrate that IGHR-CLLs have a distinct mutational profilewith recurrent mutations in BRAF and HIST1H1E genes. Interestingly, BCL2 and FBXW7mutations were significantly associated with this subgroup and almost half of BCL2, IGLL5 and HISTH1E mutations reported were previously identified in non-Hodgkin lymphomas. Notably, IGH/BCL2 rearrangements were associated with a lower mutation frequency and carried BCL2 and IGLL5 mutations, while the other IGHR-CLLs had mutations in genesrelated to poor prognosis (NOTCH1, SF3B1 and TP53) and shorter time to first treat-ment (TFT). Moreover, IGHR-CLLs patients showed a shorter TFT than CLL patients carrying 13q−, normal fluorescence in situ hybridization (FISH) and +12 CLL, NOTCH1, SF3B1, TP53, BIRC3 and BRAF werealso mutated. The presence of these mutations not only was an independent risk fac-tor within IGHR-CLLs, but also refined the prognosis of low-risk cytogenetic patients(13q−/normal FISH). Hence, our study demonstrates that IGHR-CLLs have a distinct mutational profile from the majority of CLLs and highlights the relevance of incorporating NGS and the status ofIGHby FISH analysis to refine the risk-stratification CLL model. PB John Wiley & Sons Ltd SN 0020-7136 YR 2020 FD 2020-09-24 LK https://hdl.handle.net/20.500.14352/93358 UL https://hdl.handle.net/20.500.14352/93358 LA eng NO Pérez‐Carretero C, Hernández‐Sánchez M, González T, Quijada‐Álamo M, Martín‐Izquierdo M, Hernández‐Sánchez J, et al. Chronic lymphocytic leukemia patients with IGH translocations are characterized by a distinct genetic landscape with prognostic implications. Intl Journal of Cancer 2020;147:2780–92. https://doi.org/10.1002/ijc.33235. NO Instituto de Salud Carlos III NO 'El Fondo Social Europeo invierte en tu futuro NO European Regional Development Fund NO Spanish Fondo de Investigaciones Sanitarias DS Docta Complutense RD 24 ago 2024