Pre-neoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma [WES]

ABSTRACT: Normal-cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B-lymphocytes prior to 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 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 lymphoma patients. 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 pre-neoplastic event, which challenges current understanding of lymphomagenesis and may have implications for early detection of B-cell lymphomas.

ORGANISM(S): Mus musculus

PROVIDER: GSE185156 | GEO | 2021/11/04

REPOSITORIES: GEO