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dc.contributor.author Okosun J
dc.contributor.author Bödör, Csaba
dc.contributor.author Wang J
dc.contributor.author Araf S
dc.contributor.author Yang C-Y
dc.contributor.author Pan C
dc.contributor.author Boller S
dc.contributor.author Cittaro D
dc.contributor.author Bozek M
dc.contributor.author Iqbal S
dc.contributor.author Matthews J
dc.contributor.author Wrench D
dc.contributor.author Marzec J
dc.contributor.author Tawana K
dc.contributor.author Popov N
dc.contributor.author O'Riain C
dc.contributor.author O'Shea D
dc.contributor.author Carlotti E
dc.contributor.author Davies A
dc.contributor.author Lawrie CH
dc.contributor.author Matolcsy, András
dc.contributor.author Calaminici M
dc.contributor.author Norton A
dc.contributor.author Byers RJ
dc.contributor.author Mein C
dc.contributor.author Stupka E
dc.contributor.author Lister TA
dc.contributor.author Lenz G
dc.contributor.author Montoto S
dc.contributor.author Gribben JG
dc.contributor.author Fan Y
dc.contributor.author Grosschedl R
dc.contributor.author Chelala C
dc.contributor.author Fitzgibbon J
dc.date.accessioned 2016-12-22T15:43:20Z
dc.date.available 2016-12-22T15:43:20Z
dc.date.issued 2014
dc.identifier 84890518199
dc.identifier.citation pagination=176-181; journalVolume=46; journalIssueNumber=2; journalTitle=NATURE GENETICS;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/2962
dc.identifier.uri doi:10.1038/ng.2856
dc.description.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.
dc.relation.ispartof urn:issn:1061-4036
dc.title Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma
dc.type Journal Article
dc.date.updated 2015-12-07T14:17:26Z
dc.language.rfc3066 en
dc.identifier.mtmt 2492556
dc.identifier.wos 000331208300015
dc.identifier.pubmed 24362818
dc.contributor.department SE/AOK/I/I. Sz. Patológiai és Kísérleti Rákkutató Intézet
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote Contributed equally Okosun J and Bödör C


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