{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:33:12Z","timestamp":1790375592237,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,3,17]],"date-time":"2016-03-17T00:00:00Z","timestamp":1458172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2016,4]]},"abstract":"Abstract<\/jats:title>Adult T cell leukaemia\/lymphoma (ATLL<\/jats:styled-content>) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next\u2010generation sequencing\u2010based comprehensive mutation studies have revealed recurrent somatic CCR4<\/jats:styled-content><\/jats:italic> mutations in ATLL<\/jats:styled-content>, although clinicopathological findings associated with CCR4<\/jats:styled-content><\/jats:italic> mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL<\/jats:styled-content>, were subjected to CCR4<\/jats:styled-content><\/jats:italic> mutation analysis. This sequence analysis identified mutations in 27% (30\/113) of cases of ATLL<\/jats:styled-content> and 9% (4\/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS<\/jats:styled-content>) and frameshift (FS<\/jats:styled-content>) mutations. No significant differences in clinicopathological findings were observed between ATLL<\/jats:styled-content> cases stratified by presence of CCR4<\/jats:styled-content><\/jats:italic> mutation. All ATLL<\/jats:styled-content> cases with CCR4<\/jats:styled-content><\/jats:italic> mutations exhibited cell\u2010surface CCR4<\/jats:styled-content> positivity. Semi\u2010quantitative CCR4<\/jats:styled-content> protein analysis of immunohistochemical sections revealed higher CCR4<\/jats:styled-content> expression in cases with NS<\/jats:styled-content> mutations of CCR4<\/jats:styled-content><\/jats:italic> than in cases with wild\u2010type (WT<\/jats:styled-content>) CCR4<\/jats:styled-content><\/jats:italic>. Furthermore, among ATLL<\/jats:styled-content> cases, FS<\/jats:styled-content> mutation was significantly associated with a poor prognosis, compared with NS<\/jats:styled-content> mutation and WT<\/jats:styled-content> CCR4<\/jats:styled-content><\/jats:italic>. These results suggest that CCR4<\/jats:styled-content><\/jats:italic> mutation is an important determinant of the clinical course in ATLL<\/jats:styled-content> cases, and that NS<\/jats:styled-content> and FS<\/jats:styled-content> mutations of CCR4<\/jats:styled-content><\/jats:italic> behave differently with respect to ATLL<\/jats:styled-content> pathophysiology. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4699","type":"journal-article","created":{"date-parts":[[2016,2,5]],"date-time":"2016-02-05T03:53:16Z","timestamp":1454644396000},"page":"621-626","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["CCR4<\/i> frameshift mutation identifies a distinct group of adult T cell leukaemia\/lymphoma with poor prognosis"],"prefix":"10.1002","volume":"238","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7001-0106","authenticated-orcid":false,"given":"Noriaki","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Pathology Kurume University School of Medicine Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Miyoshi","sequence":"additional","affiliation":[{"name":"Department of Pathology Kurume University School of Medicine 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