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Preneoplastic somatic mutations including MYD88^L265P in lymphoplasmacytic lymphoma.

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 MYD88^L265P 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, MYD88^L265P is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas.

SUBMITTER: Rodriguez S

PROVIDER: S-EPMC8769557 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Pre-neoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma

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