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We used targeted sequencing of genes altered in hematologic malignancies, including DNA coding sequence for 405 genes, noncoding sequence for 31 genes, and RNA coding sequence for 265 genes (FoundationOne-Heme). Short variants, rearrangements, and copy number alterations were determined. We studied 198 samples (114 de novo, 58 previously treated, and 26 large-cell transformation from follicular lymphoma). Median number of GAs per case was 6, with 97% of patients harboring at least one alteration. Recurrent GAs were detected in genes with established roles in DLBCL pathogenesis (e.g. <jats:italic>MYD88<\/jats:italic>, <jats:italic>CREBBP<\/jats:italic>, <jats:italic>CD79B<\/jats:italic>, <jats:italic>EZH2<\/jats:italic>), as well as notable differences compared to prior studies such as inactivating mutations in <jats:italic>TET2<\/jats:italic> (5%). Less common GAs identified potential targets for approved or investigational therapies, including <jats:italic>BRAF<\/jats:italic>, <jats:italic>CD274<\/jats:italic> (PD-L1), <jats:italic>IDH2<\/jats:italic>, and <jats:italic>JAK1\/2<\/jats:italic>. <jats:italic>TP53<\/jats:italic> mutations were more frequently observed in relapsed\/refractory DLBCL, and predicted for lack of response to first-line chemotherapy, identifying a subset of patients that could be prioritized for novel therapies. Overall, 90% (<jats:italic>n<\/jats:italic>\u2009=\u2009169) of the patients harbored a GA which could be explored for therapeutic intervention, with 54% (<jats:italic>n<\/jats:italic>\u2009=\u2009107) harboring more than one putative target.<\/jats:p>","DOI":"10.1038\/s41408-018-0089-0","type":"journal-article","created":{"date-parts":[[2018,6,12]],"date-time":"2018-06-12T16:13:31Z","timestamp":1528820011000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Integrated DNA\/RNA targeted genomic profiling of diffuse large B-cell lymphoma using a clinical assay"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9046-6549","authenticated-orcid":false,"given":"Andrew M.","family":"Intlekofer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7883-289X","authenticated-orcid":false,"given":"Erel","family":"Joffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie L.","family":"Batlevi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4523-7995","authenticated-orcid":false,"given":"Patrick","family":"Hilden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatraman E.","family":"Seshan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Zelenetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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