: 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.

Rodriguez, S., Celay, J., Goicoechea, I., Jimenez, C., Botta, C., Garcia-Barchino, M., et al. (2022). Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma. SCIENCE ADVANCES, 8(3), eabl4644 [10.1126/sciadv.abl4644].

Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma

Botta, Cirino;
2022-01-21

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.
Rodriguez, S., Celay, J., Goicoechea, I., Jimenez, C., Botta, C., Garcia-Barchino, M., et al. (2022). Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma. SCIENCE ADVANCES, 8(3), eabl4644 [10.1126/sciadv.abl4644].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/531181
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