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

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

PROVIDER: PRJNA767843 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16151300_1.fastq.gz	Fastqsanger.gz
	SRR16151300_2.fastq.gz	Fastqsanger.gz
	SRR16151301_1.fastq.gz	Fastqsanger.gz
	SRR16151301_2.fastq.gz	Fastqsanger.gz
	SRR16151277_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

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Pre-neoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma

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Pre-neoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma

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