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To address this issue, we performed whole\u2010exome sequencing of normal\/tumoral DNA pairs in 14 relapsed\/refractory (R\/R) patients subclassified by full\u2010transcriptome arrays (six activated B\u2010cell like, three germinal center B\u2010cell like, and five primary mediastinal B\u2010cell lymphomas), from the LNH\u201003 LYSA clinical trial program. Aside from well\u2010known DLBCL features, gene and pathway level recurrence analyses proposed several interesting leads including <jats:italic>TBL1XR1<\/jats:italic> and activating mutations in <jats:italic>IRF4<\/jats:italic> or in the insulin regulation pathway. Sequencing\u2010based copy number analysis defined 23 short recurrently altered regions involving genes such as <jats:italic>REL<\/jats:italic>, <jats:italic>CDKN2A<\/jats:italic>, <jats:italic>HYAL2<\/jats:italic>, and <jats:italic>TP53<\/jats:italic>. Moreover, it highlighted mutations in genes such as <jats:italic>GNA13<\/jats:italic>, <jats:italic>CARD11, MFHAS1<\/jats:italic>, and <jats:italic>PCLO<\/jats:italic> as associated with secondary variant allele amplification events. The five primary mediastinal B\u2010cell lymphomas (PMBL), while unexpected in a R\/R cohort, showed a significantly higher mutation rate (<jats:italic>P =<\/jats:italic> 0.003) and provided many insights on this classical Hodgkin lymphoma related subtype. Novel genes such as <jats:italic>XPO1<\/jats:italic>, <jats:italic>MFHAS1<\/jats:italic>, and <jats:italic>ITPKB<\/jats:italic> were found particularly mutated, along with various cytokine\u2010based signaling pathways. Among these analyses, somatic events in the NF\u2010\u03baB pathway were found preponderant in the three DLBCL subtypes, confirming its major implication in DLBCL aggressiveness and pinpointing several new candidate genes. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22328","type":"journal-article","created":{"date-parts":[[2015,11,26]],"date-time":"2015-11-26T07:57:57Z","timestamp":1448524677000},"page":"251-267","source":"Crossref","is-referenced-by-count":85,"title":["Whole exome sequencing of relapsed\/refractory patients expands the repertoire of somatic mutations in diffuse large <scp>B<\/scp>\u2010cell lymphoma"],"prefix":"10.1002","volume":"55","author":[{"given":"Sylvain","family":"Mareschal","sequence":"first","affiliation":[{"name":"INSERM U918, Centre Henri Becquerel Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Dubois","sequence":"additional","affiliation":[{"name":"INSERM U918, Centre Henri Becquerel 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