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    Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma.

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    Authors
    Okosun, J
    Bödör, C
    Wang, J
    Araf, S
    Yang, C
    Pan, C
    Boller, S
    Cittaro, D
    Bozek, M
    Iqbal, S
    Matthews, J
    Wrench, D
    Marzec, J
    Tawana, K
    Popov, N
    O'Riain, C
    O'Shea, D
    Carlotti, E
    Davies, A
    Lawrie, C
    Matolcsy, A
    Calaminici, M
    Norton, Andrew J
    Byers, R
    Mein, C
    Stupka, E
    Lister, T
    Lenz, G
    Montoto, S
    Gribben, J
    Fan, Y
    Grosschedl, R
    Chelala, C
    Fitzgibbon, J
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    Issue Date
    2014-02
    
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    Abstract
    Follicular lymphoma is an incurable malignancy, with transformation to an aggressive subtype representing a critical event during disease progression. Here we performed whole-genome or whole-exome sequencing on 10 follicular lymphoma-transformed follicular lymphoma pairs followed by deep sequencing of 28 genes in an extension cohort, and we report the key events and evolutionary processes governing tumor initiation and transformation. Tumor evolution occurred through either a 'rich' or 'sparse' ancestral common progenitor clone (CPC). We identified recurrent mutations in linker histone, JAK-STAT signaling, NF-κB signaling and B cell developmental genes. Longitudinal analyses identified early driver mutations in chromatin regulator genes (CREBBP, EZH2 and KMT2D (MLL2)), whereas mutations in EBF1 and regulators of NF-κB signaling (MYD88 and TNFAIP3) were gained at transformation. Collectively, this study provides new insights into the genetic basis of follicular lymphoma and the clonal dynamics of transformation and suggests that personalizing therapies to target key genetic alterations in the CPC represents an attractive therapeutic strategy.
    Citation
    Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. 2014, 46 (2):176-81 Nat Genet
    Journal
    Nature Genetics
    URI
    http://hdl.handle.net/10541/312434
    DOI
    10.1038/ng.2856
    PubMed ID
    24362818
    Type
    Article
    Language
    en
    ISSN
    1546-1718
    ae974a485f413a2113503eed53cd6c53
    10.1038/ng.2856
    Scopus Count
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