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The genetic basis underlying MHG-DLBCL and their aggressive clinical behaviour remain unknown. We investigated 697 cases of DLBCL, particularly those with\n                    <jats:italic>MYC<\/jats:italic>\n                    \/\n                    <jats:italic>BCL2<\/jats:italic>\n                    -DH (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200962) by targeted sequencing and gene expression profiling. We showed that DLBCL with\n                    <jats:italic>MYC<\/jats:italic>\n                    \/\n                    <jats:italic>BCL2<\/jats:italic>\n                    -DH, and those with\n                    <jats:italic>BCL2<\/jats:italic>\n                    translocation, harbour the characteristic mutation signatures that are associated with follicular lymphoma and its high-grade transformation. We identified frequent\n                    <jats:italic>MYC<\/jats:italic>\n                    hotspot mutations that affect the phosphorylation site (T58) and its adjacent amino acids, which are important for MYC protein degradation. These\n                    <jats:italic>MYC<\/jats:italic>\n                    mutations were seen in a subset of cases with\n                    <jats:italic>MYC<\/jats:italic>\n                    translocation, but predominantly in those of MHG. The mutations were more frequent in double-hit lymphomas with IG as the\n                    <jats:italic>MYC<\/jats:italic>\n                    translocation partner, and were associated with higher MYC protein expression and poor patient survival. DLBCL with\n                    <jats:italic>MYC<\/jats:italic>\n                    \/\n                    <jats:italic>BCL2<\/jats:italic>\n                    -DH and those with\n                    <jats:italic>BCL2<\/jats:italic>\n                    translocation alone are most likely derived from follicular lymphoma or its precursor lesion, and acquisition of\n                    <jats:italic>MYC<\/jats:italic>\n                    pathogenic mutations may augment MYC function, resulting in aggressive clinical behaviour.\n                  <\/jats:p>","DOI":"10.1038\/s41375-019-0691-6","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T13:03:04Z","timestamp":1576501384000},"page":"1329-1341","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["Distinct genetic changes reveal evolutionary history and heterogeneous molecular grade of DLBCL with MYC\/BCL2 double-hit"],"prefix":"10.1038","volume":"34","author":[{"given":"Francesco","family":"Cucco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Barrans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chulin","family":"Sha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Clipson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Crouch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Dobson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe Sneath","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Care","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Cummin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Caddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Schuh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jude","family":"Fitzgibbon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Painter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eve","family":"Roman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reuben","family":"Tooze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Burton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0519-3820","authenticated-orcid":false,"given":"David R.","family":"Westhead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W. 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