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Here we performed the first whole-exome sequencing study of WM patients who evolved to DLBCL and report the genetic alterations that may drive this process. Our results demonstrate that transformation depends on the frequency and specificity of acquired variants, rather than on the duration of its evolution. We did not find a common pattern of mutations at diagnosis or transformation; however, there were certain abnormalities that were present in a high proportion of clonal tumor cells and conserved during this transition, suggesting that they have a key role as early drivers. In addition, recurrent mutations gained in some genes at transformation (for example, <jats:italic>PIM1<\/jats:italic>, <jats:italic>FRYL<\/jats:italic> and <jats:italic>HNF1B<\/jats:italic>) represent cooperating events in the selection of the clones responsible for disease progression. Detailed comparison reveals the gene abnormalities at diagnosis and transformation to be consistent with a branching model of evolution. Finally, the frequent mutation observed in the <jats:italic>CD79B<\/jats:italic> gene in this specific subset of patients implies that it is a potential biomarker predicting transformation in WM.<\/jats:p>","DOI":"10.1038\/bcj.2017.72","type":"journal-article","created":{"date-parts":[[2017,8,25]],"date-time":"2017-08-25T13:22:02Z","timestamp":1503667322000},"page":"e591-e591","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["From Waldenstr\u00f6m\u2019s macroglobulinemia to aggressive diffuse large B-cell lymphoma: a whole-exome analysis of abnormalities leading to transformation"],"prefix":"10.1038","volume":"7","author":[{"given":"C","family":"Jim\u00e9nez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Alonso-\u00c1lvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Alcoceba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G R","family":"Ord\u00f3\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Garc\u00eda-\u00c1lvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M I","family":"Prieto-Conde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M C","family":"Chill\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Balanzategui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Corral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L A","family":"Mar\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N C","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Puig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M E","family":"Sarasquete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Garc\u00eda-Sanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,25]]},"reference":[{"key":"BFbcj201772_CR1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1053\/sonc.2003.50082","volume":"30","author":"RG Owen","year":"2003","unstructured":"Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML et al. 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