1. Preneoplastic somatic mutations including MYD88L²⁶⁵P in lymphoplasmacytic lymphoma
- Author
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Rodriguez, Sara, Celay, Jon, Goicoechea, Ibai, Jimenez, Cristina, Botta, Cirino, Garcia-Barchino, Maria-José, Garces, Juan-Jose, Larrayoz, Marta, Santos, Susana, Alignani, Diego, Vilas-Zornoza, Amaia, Perez, Cristina, Garate, Sonia, Sarvide, Sarai, Lopez, Aitziber, Reinhardt, Christian, Carrasco, Yolanda R., Sanchez-Garcia, Isidro, Larrayoz, Maria-Jose, Calasanz, Maria-Jose, Panizo, Carlos, Prosper, Felipe, Lamo-Espinosa, Jose-Maria, Motta, Marina, Tucci, Alessandra, Sacco, Antonio, Gentile, Massimo, Duarte, Sara, Vitoria, Helena, Geraldes, Catarina, Paiva, Artur, Puig, Noemi, Garcia-Sanz, Ramon, Roccaro, Aldo M., Fuerte, Gema, San Miguel, Jesus F., Martinez-Climent, Jose-Angel, and Paiva, Bruno
- Subjects
hemic and lymphatic diseases ,Medizin - Abstract
Normal cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B lymphocytes before lymphoma remains uncertain. We sequenced multiple stages of the B lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of the high prevalence of mutated MYD88. We observed similar accumulation of random mutations in B lineages from both cohorts and unexpectedly found MYD88L²⁶⁵P in normal precursor and mature B lymphocytes from patients with lymphoma. We uncovered genetic and transcriptional pathways driving malignant transformation and leveraged these to model lymphoplasmacytic lymphoma in mice, based on mutated MYD88 in B cell precursors and BCL2 overexpression. Thus, MYD88L²⁶⁵P is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas. CA extern
- Published
- 2022