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- W4376641569 abstract "<div>Abstract<p>Follicular lymphomas (FL) are characterized by <i>BCL2</i> translocations, often detectable in blood years before FL diagnosis, but also observed in aging healthy individuals, suggesting additional lesions are required for lymphomagenesis. We directly characterized early cooperating mutations by ultradeep sequencing of prediagnostic blood and tissue specimens from 48 subjects who ultimately developed FL. Strikingly, <i>CREBBP</i> lysine acetyltransferase (KAT) domain mutations were the most commonly observed precursor lesions, and largely distinguished patients developing FL (14/48, 29%) from healthy adults with or without detected <i>BCL2</i> rearrangements (0/13, <i>P</i> = 0.03 and 0/20, <i>P</i> = 0.007, respectively). <i>CREBBP</i> variants were detectable a median of 5.8 years before FL diagnosis, were clonally selected in FL tumors, and appeared restricted to the committed B-cell lineage. These results suggest that mutations affecting the <i>CREBBP</i> KAT domain are common lesions in FL cancer precursor cells (CPC), with the potential for discriminating subjects at risk of developing FL or monitoring residual disease.</p>Significance:<p>Our study provides direct evidence for recurrent genetic aberrations preceding FL diagnosis, revealing the combination of <i>BCL2</i> translocation with <i>CREBBP</i> KAT domain mutations as characteristic committed lesions of FL CPCs. Such prediagnostic mutations are detectable years before clinical diagnosis and may help discriminate individuals at risk for lymphoma development.</p></div>" @default.
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- W4376641569 date "2023-05-16" @default.
- W4376641569 modified "2023-09-28" @default.
- W4376641569 title "Data from Tracing Founder Mutations in Circulating and Tissue-Resident Follicular Lymphoma Precursors" @default.
- W4376641569 doi "https://doi.org/10.1158/2159-8290.c.6649130.v1" @default.
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