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Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma

Title: Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma
Authors: Rodriguez, Sara; Celay, Jon; Goicoechea, Ibai; Jimenez, Cristina; Botta, Cirino; Garcia-Barchino, Maria-José; Garces, Juan-Jose; Larrayoz, Marta; Santos, Susana; Alignani, Diego; Vilas-Zornoza, Amaia; Perez, Cristina; Garate, Sonia; Sarvide, Sarai; Lopez, Aitziber; Reinhardt, Hans-Christian; Carrasco, Yolanda R; Sanchez-Garcia, Isidro; Larrayoz, Maria-Jose; Calasanz, Maria-Jose; Panizo, Carlos; Prosper, Felipe; Lamo-Espinosa, Jose-Maria; Motta, Marina; Tucci, Alessandra; Sacco, Antonio; Gentile, Massimo; Duarte, Sara; Vitoria, Helena; Geraldes, Catarina; Paiva, Artur; Puig, Noemi; Garcia-Sanz, Ramon; Roccaro, Aldo M; Fuerte, Gema; San Miguel, Jesus F; Martinez-Climent, Jose-Angel; Paiva, Bruno
Contributors: Rodriguez, Sara; Celay, Jon; Goicoechea, Ibai; Jimenez, Cristina; Botta, Cirino; Garcia-Barchino, Maria-José; Garces, Juan-Jose; Larrayoz, Marta; Santos, Susana; Alignani, Diego; Vilas-Zornoza, Amaia; Perez, Cristina; Garate, Sonia; Sarvide, Sarai; Lopez, Aitziber; Reinhardt, Hans-Christian; Carrasco, Yolanda R; Sanchez-Garcia, Isidro; Larrayoz, Maria-Jose; Calasanz, Maria-Jose; Panizo, Carlo; Prosper, Felipe; Lamo-Espinosa, Jose-Maria; Motta, Marina; Tucci, Alessandra; Sacco, Antonio; Gentile, Massimo; Duarte, Sara; Vitoria, Helena; Geraldes, Catarina; Paiva, Artur; Puig, Noemi; Garcia-Sanz, Ramon; Roccaro, Aldo M; Fuerte, Gema; San Miguel, Jesus F; Martinez-Climent, Jose-Angel; Paiva, Bruno
Publication Year: 2022
Collection: IRIS Università degli Studi di Palermo
Subject Terms: lymphoplasmacytic lymphoma; MYD88; B cell lymphoma; single cell
Description: 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.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/35044826; info:eu-repo/semantics/altIdentifier/wos/WOS:000745886100027; volume:8; issue:3; firstpage:eabl4644; numberofpages:19; journal:SCIENCE ADVANCES; http://hdl.handle.net/10447/531181
DOI: 10.1126/sciadv.abl4644
Availability: http://hdl.handle.net/10447/531181; https://doi.org/10.1126/sciadv.abl4644
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.CD959665
Database: BASE