{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:42:53Z","timestamp":1790797373702,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,7,29]],"date-time":"2017-07-29T00:00:00Z","timestamp":1501286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["15Ack0106014h0002"],"award-info":[{"award-number":["15Ack0106014h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["15im0210102h0001"],"award-info":[{"award-number":["15im0210102h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2017,9]]},"abstract":"Adult T\u2010cell leukemia\/lymphoma (ATL<\/jats:styled-content>) is a peripheral T\u2010cell neoplasm with a dismal prognosis. It is caused by human T\u2010cell leukemia virus type\u20101 (HTLV<\/jats:styled-content>\u20101) retrovirus. A long latency period from HTLV<\/jats:styled-content>\u20101 infection to ATL<\/jats:styled-content> onset suggests that not only HTLV<\/jats:styled-content>\u20101 proteins, such as Tax and HBZ<\/jats:styled-content>, but also additional genetic and\/or epigenetic events are required for ATL<\/jats:styled-content> development. Although many studies have demonstrated the biological functions of viral genes, alterations of cellular genes associated with ATL<\/jats:styled-content> have not been fully investigated. Recently, a large\u2010scale integrated genetic analysis revealed the entire landscape of somatic aberrations in ATL<\/jats:styled-content>. This neoplasm is characterized by frequent gain\u2010of\u2010function alterations in components of the T\u2010cell receptor\/NF<\/jats:styled-content>\u2010\u03baB signaling pathway, including activating mutations in the PLCG<\/jats:styled-content>1<\/jats:italic>, PRKCB<\/jats:styled-content><\/jats:italic>, CARD<\/jats:styled-content>11<\/jats:italic> and VAV<\/jats:styled-content>1<\/jats:italic> genes, and CTLA<\/jats:styled-content>4\u2010CD<\/jats:styled-content>28<\/jats:italic> and ICOS<\/jats:styled-content>\u2010CD<\/jats:styled-content>28<\/jats:italic> fusions. Importantly, molecules associated with immune surveillance, such as HLA<\/jats:styled-content>\u2010A\/B<\/jats:italic>, CD<\/jats:styled-content>58<\/jats:italic> and FAS<\/jats:styled-content><\/jats:italic>, are affected recurrently. Among them, one notable lesion occurs as frequent structural variations that truncate the PD<\/jats:styled-content>\u2010L1<\/jats:italic> 3\u2032\u2010untranslated region, leading to its overexpression. Other genetic targets include transcription factors (IRF<\/jats:styled-content>4<\/jats:italic>, IKZF<\/jats:styled-content>2<\/jats:italic>, and GATA<\/jats:styled-content>3<\/jats:italic>) and chemokine receptors (CCR<\/jats:styled-content>4<\/jats:italic>, CCR<\/jats:styled-content>7<\/jats:italic> and GPR<\/jats:styled-content>183<\/jats:italic>), which are functionally relevant in normal T cells. A substantial proportion of ATL<\/jats:styled-content> cases show widespread accumulation of repressive epigenetic changes, such as trimethylation of histone H3 lysine 27 and DNA<\/jats:styled-content> hypermethylation of CpG islands, which coordinately modulate multiple pathways, including Cys2\u2010His2 zinc finger genes involved in silencing retroelements. Here we review the current understanding of the genetic\/epigenetic aberrations in ATL<\/jats:styled-content>, focusing on their relevance in its molecular pathogenesis.<\/jats:p>","DOI":"10.1111\/cas.13303","type":"journal-article","created":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T11:36:42Z","timestamp":1497872202000},"page":"1719-1725","source":"Crossref","is-referenced-by-count":85,"title":["Genetic alterations in adult T\u2010cell leukemia\/lymphoma"],"prefix":"10.1111","volume":"108","author":[{"given":"Yasunori","family":"Kogure","sequence":"first","affiliation":[{"name":"Department of Pathology and Tumor Biology Graduate School of Medicine Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8263-9902","authenticated-orcid":false,"given":"Keisuke","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Department of Pathology and Tumor Biology Graduate School of Medicine Kyoto 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