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We employed targeted next\u2010generation sequencing and single nucleotide polymorphism array for 89 patients with ATLL in Okinawa, the southernmost islands in Japan, where the frequency of HTLV\u20101 <jats:italic>tax<\/jats:italic> subgroup\u2010A (HTLV\u20101\u2010<jats:italic>tax<\/jats:italic>A) is notably higher than that in mainland Japan, where most ATLL cases have HTLV\u20101\u2010<jats:italic>tax<\/jats:italic>B, and compared the results with previously reported genomic landscapes of ATLL in mainland Japan and the USA. Okinawan patients exhibited similar mutation profiles to mainland Japanese patients, with frequent alterations in TCR\/NF\u2010\u0138B (eg, <jats:italic>PRKCB<\/jats:italic>, <jats:italic>PLCG1<\/jats:italic>, and <jats:italic>CARD11<\/jats:italic>) and T\u2010cell trafficking pathways (<jats:italic>CCR4<\/jats:italic> and <jats:italic>CCR7<\/jats:italic>), in contrast with North American patients who exhibited a predominance of epigenome\u2010associated gene mutations. Some mutations, especially <jats:italic>GATA3<\/jats:italic> and <jats:italic>RHOA<\/jats:italic>, were detected more frequently in Okinawan patients than in mainland Japanese patients. Compared to HTLV\u20101\u2010<jats:italic>tax<\/jats:italic>B, HTLV\u20101\u2010<jats:italic>tax<\/jats:italic>A was significantly dominant in Okinawan patients with these mutations (<jats:italic>GATA3<\/jats:italic>, 34.1% vs 14.6%, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.044; <jats:italic>RHOA<\/jats:italic>, 24.4% vs 6.3%, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.032), suggesting the contribution of viral strains to these mutation frequencies. From a clinical viewpoint, we identified a significant negative impact of biallelic inactivation of <jats:italic>PRDM1<\/jats:italic> (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.027) in addition to the previously reported <jats:italic>PRKCB<\/jats:italic> mutations, indicating the importance of integrated genetic analysis. This study suggests that heterogeneous genetic abnormalities in ATLL depend on the viral strain as well as on the ethnic background. This warrants the need to develop therapeutic interventions considering regional characteristics.<\/jats:p>","DOI":"10.1111\/cas.14806","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T04:23:01Z","timestamp":1610684581000},"page":"1300-1309","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Genetic profile of adult T\u2010cell leukemia\/lymphoma in Okinawa: Association with prognosis, ethnicity, and HTLV\u20101 strains"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2411-2539","authenticated-orcid":false,"given":"Shugo","family":"Sakihama","sequence":"first","affiliation":[{"name":"Department of Pathology and Cell Biology Graduate School of Medicine University of the Ryukyus Nishihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuho","family":"Morichika","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine) Graduate School of Medicine University of the Ryukyus Nishihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumiko","family":"Saito","sequence":"additional","affiliation":[{"name":"Life Science Analytic Center Life Science Business Office Corporate Technology Planning Division Toshiba Corporation Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Miyara","sequence":"additional","affiliation":[{"name":"Faculty of Health and Nutrition Okinawa University Naha Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Miyagi","sequence":"additional","affiliation":[{"name":"Department of Hematology Heartlife Hospital Nakagusuku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department 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