{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T21:49:30Z","timestamp":1775339370696,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T00:00:00Z","timestamp":1591315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diffuse large B\u2010cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R\u2010CHOP. We performed capture\u2010based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma\u2010related genes. Subsequently, 81 treatment\u2010na\u00efve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included <jats:italic>IGH<\/jats:italic> fusion (69%), <jats:italic>PIM1<\/jats:italic>(33%), <jats:italic>MYD88<\/jats:italic> (29%), <jats:italic>BCL2<\/jats:italic> (29%), <jats:italic>TP53<\/jats:italic> (29%), <jats:italic>CD79B<\/jats:italic> (25%) and <jats:italic>KMT2D<\/jats:italic> (24%). Patients with <jats:italic>TP53<\/jats:italic> mutations were more likely to have primary refractory disease (87.0% vs 50.0%, <jats:italic>P<\/jats:italic> = .009). For those with <jats:italic>TP53<\/jats:italic> disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, <jats:italic>BCL\u20102<\/jats:italic> somatic hypermutation was only seen in patients without primary refractory disease (<jats:italic>P<\/jats:italic> = .014). In multivariate analysis, <jats:italic>BCL\u20102<\/jats:italic> amplification (hazard ratio [HR] = 2.94, <jats:italic>P<\/jats:italic> = .022), <jats:italic>B2M<\/jats:italic> mutation (HR = 2.99, <jats:italic>P<\/jats:italic> = .017) and <jats:italic>TP53<\/jats:italic> mutation (HR = 3.19, <jats:italic>P<\/jats:italic> &lt; .001) were independently associated with shorter time to progression (TTP). Furthermore, <jats:italic>TP53<\/jats:italic> mutations was correlated with worse overall survival (<jats:italic>P<\/jats:italic> = .049). Next, we investigated mutation landscape in patients with wild\u2010type (WT) <jats:italic>TP5<\/jats:italic>3 (n = 58) and found that patients harboring <jats:italic>MYD88<\/jats:italic> L265P had significantly inferior TTP than those with WT or non\u2010265P (<jats:italic>P<\/jats:italic> = .046). Our study reveals the mutation spectrum of treatment\u2010naive Chinese DLBCL patients. It also confirms the clinical significance of <jats:italic>TP53<\/jats:italic> mutations and indicates the prognostic value of <jats:italic>MYD88<\/jats:italic> L265P in <jats:italic>TP53<\/jats:italic> WT patients.<\/jats:p>","DOI":"10.1002\/ijc.33049","type":"journal-article","created":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T08:49:39Z","timestamp":1589359779000},"page":"2611-2620","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Molecular profiling of Chinese <scp>R\u2010CHOP<\/scp> treated <scp>DLBCL<\/scp> patients: Identifying a high\u2010risk subgroup"],"prefix":"10.1002","volume":"147","author":[{"given":"Shiyu","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Suzhou Municipal Hospital Affiliated Suzhou Hospital of Nanjing Medical University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Suzhou Municipal Hospital Affiliated Suzhou Hospital of Nanjing Medical University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianming","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Suzhou Municipal Hospital Affiliated Suzhou Hospital of Nanjing Medical University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanlu","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianliang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohui","family":"He","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Gui","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"Burning Rock Biotech  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Lin","sequence":"additional","affiliation":[{"name":"Burning Rock Biotech  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Han\u2010Zhang","sequence":"additional","affiliation":[{"name":"Burning Rock Biotech  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8685-6744","authenticated-orcid":false,"given":"Yuankai","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.148809"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21357"},{"key":"e_1_2_11_4_1","first-page":"111","article-title":"Distribution pattern of lymphoma subtypes in China: a nationwide multicenter study of 10002 cases","volume":"11","author":"Li XQ LG","year":"2012","journal-title":"J Diagn Concepts Pract"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011795"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-276246"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2011.1.498"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.1618"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3816\/CLML.2010.n.017"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2015.213"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199309303291402"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-038257"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-09-524108"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-276766"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/35000501"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012914"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.60.2383"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.3660"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1545"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2015.01.005"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1525"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1922"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.71.7603"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10351"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.027"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-296244"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-10-460063"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13065"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-02-072082"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14080"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.184"},{"key":"e_1_2_11_32_1","first-page":"1707","article-title":"High frequency and prognostic value of MYD88 L265P mutation in diffuse large B\u2010cell lymphoma with R\u2010CHOP treatment","volume":"15","author":"Yu S","year":"2018","journal-title":"Oncol Lett"},{"key":"e_1_2_11_33_1","volume-title":"WHO Classification of Tumors of Haematopoietic and Lymphoid Tissue","author":"Swerdlow SHCE","year":"2008"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.2403"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.08.028"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.892"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-366062"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V79.10.2701.bloodjournal79102701"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199708213370804"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-433334"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30838"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01998-5"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2011.31"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801445"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2013.28"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-747022"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.33049","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.33049","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.33049","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.33049","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T15:44:26Z","timestamp":1693842266000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.33049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,5]]},"references-count":45,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/ijc.33049"],"URL":"https:\/\/doi.org\/10.1002\/ijc.33049","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,5]]},"assertion":[{"value":"2019-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}