Scientific publications
Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma
Sara Rodriguez 1 , Jon Celay 1 , Ibai Goicoechea 1 , Cristina Jimenez 2 , Cirino Botta 3 , Maria-José Garcia-Barchino 1 , Juan-Jose Garces 1 , Marta Larrayoz 1 , Susana Santos 4 , Diego Alignani 1 , Amaia Vilas-Zornoza 1 , Cristina Perez 1 , Sonia Garate 1 , Sarai Sarvide 1 , Aitziber Lopez 1 , Hans-Christian Reinhardt 5 , Yolanda R Carrasco 6 , Isidro Sanchez-Garcia 7 , Maria-Jose Larrayoz 1 , Maria-Jose Calasanz 1 , Carlos Panizo 1 , Felipe Prosper 1 , Jose-Maria Lamo-Espinosa 1 , Marina Motta 8 , Alessandra Tucci 8 , Antonio Sacco 9 , Massimo Gentile 10 , Sara Duarte 4 , Helena Vitoria 11 , Catarina Geraldes 4 , Artur Paiva 4 , Noemi Puig 2 , Ramon Garcia-Sanz 2 , Aldo M Roccaro 9 , Gema Fuerte 12 , Jesus F San Miguel 1 , Jose-Angel Martinez-Climent 1 , Bruno Paiva 1
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 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.
CITATION Sci Adv. 2022 Jan 21;8(3):eabl4644. doi:10.1126/sciadv.abl4644. Epub 2022 Jan 19
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