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| Status |
Public on Nov 04, 2021 |
| Title |
Pre-neoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma [scRNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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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| |
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| Overall design |
single-cell RNA and BCR sequencing (scRNA/BCRseq) in a total of 40,169 B cells and PCs from three patients with IgM MGUS and two with LPL/WM
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| |
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| Contributor(s) |
Goicoechea I, Rodriguez S, Paiva B |
| Citation(s) |
35044826 |
| Submission date |
Oct 01, 2021 |
| Last update date |
Feb 05, 2022 |
| Contact name |
Ibai Goicoechea |
| E-mail(s) |
igoroz@unav.es
|
| Phone |
948194700
|
| Organization name |
Universidad de Navarra
|
| Street address |
Centro de Investigación Médica Aplicada (CIMA) Avenida Pío XII, 55
|
| City |
Pamplona |
| State/province |
Navarra |
| ZIP/Postal code |
31008 |
| Country |
Spain |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE185158 |
Pre-neoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma |
|
| Relations |
| BioProject |
PRJNA767844 |
| SRA |
SRP339660 |
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