{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:20:50Z","timestamp":1790601650800,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Li\u2010Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome, and the majority of patients with LFS have been identified with germline variants in the <jats:italic>p53<\/jats:italic> tumor suppressor (<jats:italic>TP53<\/jats:italic>) gene. In the past three decades, considerable case reports of <jats:italic>TP53<\/jats:italic> germline variants have been published in Japan. To the best of our knowledge, there have been no large\u2010scale studies of Japanese patients with LFS. In this study, we aimed to identify Japanese patients with <jats:italic>TP53<\/jats:italic> germline variants and to reveal the characteristics of LFS in Japan. We collected reported cases by reviewing the medical literature and cases diagnosed at the institutions of the authors. We identified 68 individuals from 48 families with <jats:italic>TP53<\/jats:italic> germline pathogenic or likely pathogenic variants. Of the 48 families, 35 (72.9%) had missense variants, most of which were located within the DNA\u2010binding loop. A total of 128 tumors were identified in the 68 affected individuals. The 128 tumor sites were as follows: breast, 25; bones, 16; brain, 12; hematological, 11; soft tissues, 10; stomach, 10; lung, 10; colorectum, 10; adrenal gland, 9; liver, 4; and others, 11. Unique phenotype patterns of LFS were shown in Japan in comparison with those in a large national LFS cohort study in France. Above all, a higher frequency of patients with stomach cancer was observed in Japanese <jats:italic>TP53<\/jats:italic> germline variant carriers. These results may provide useful information for the clinical management of LFS in Japan.<\/jats:p>","DOI":"10.1111\/cas.14919","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T09:05:26Z","timestamp":1619859926000},"page":"2821-2834","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Characteristics of Li\u2010Fraumeni syndrome in Japan: A review study by the special committee of JSHT"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8836-8333","authenticated-orcid":false,"given":"Michinori","family":"Funato","sequence":"first","affiliation":[{"name":"Department of Clinical Research National Hospital Organization Nagara Medical Center Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3278-2911","authenticated-orcid":false,"given":"Yukiko","family":"Tsunematsu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Juntendo University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3579-634X","authenticated-orcid":false,"given":"Fumito","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics National Cancer Center Research Institute Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7496-4289","authenticated-orcid":false,"given":"Chieko","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Juntendo University School of Medicine Tokyo Japan"},{"name":"Medical Information &amp; Genetic Counseling Division FMC Tokyo Clinic Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7325-5950","authenticated-orcid":false,"given":"Tadashi","family":"Kumamoto","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7580-9184","authenticated-orcid":false,"given":"Masatoshi","family":"Takagi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Developmental Biology Graduate School Tokyo Medical and Dental University (TMDU) Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4860-1687","authenticated-orcid":false,"given":"Shunsuke","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology Juntendo University Graduate School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0779-3088","authenticated-orcid":false,"given":"Haruhiko","family":"Sugimura","sequence":"additional","affiliation":[{"name":"Department of Tumor Pathology Hamamatsu University School of Medicine Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1087-9851","authenticated-orcid":false,"given":"Kazuo","family":"Tamura","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Master of Science Graduate School of Science and Engineering Research Kindai University Higashiosaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-71-4-747"},{"key":"e_1_2_7_3_1","first-page":"5358","article-title":"A cancer family syndrome in twenty\u2010four kindreds","volume":"48","author":"Li FP","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1978757"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23035"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31821628b6"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.10.014"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.073429"},{"key":"e_1_2_7_9_1","first-page":"83","article-title":"Germ\u2010line p53 mutations predispose to a wide spectrum of early\u2010onset cancers","volume":"10","author":"Nichols KE","year":"2001","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-012-1993-9"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204621"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-013-1439-8"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2532"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28507"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.5052"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.1.43"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.6959"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.5728"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30248"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.166"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0633-8"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2017.01.002"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.60"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-019-00140-w"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.1968"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70119-X"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30249-2"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/84.9.703"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199205143262001"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(93)90187-E"},{"key":"e_1_2_7_31_1","first-page":"1231","article-title":"Predominantly tumor\u2010limited expression of a mutant allele in a Japanese family carrying a germline p53 mutation","volume":"9","author":"Horio Y","year":"1994","journal-title":"Oncogene"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050086"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/28.10.631"},{"key":"e_1_2_7_34_1","first-page":"563","article-title":"A Li\u2010Fraumeni syndrome family","volume":"103","author":"Konno K","year":"1999","journal-title":"Jpn J Pediatr Soc"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/29.10.513"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hye070"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.2.304"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.COC.0000054534.43117.76"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1297\/cpe.13.25"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.44.490"},{"key":"e_1_2_7_41_1","first-page":"53","article-title":"A case of multiple primary malignant tumors with germline mutation of the TP53 gene","volume":"6","author":"Tamura K","year":"2006","journal-title":"J Fam Tumor"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm175"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-007-0692-8"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24432"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22542"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyq045"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20878"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00595-010-4359-0"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24269"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.21912"},{"key":"e_1_2_7_51_1","first-page":"499","article-title":"Radiation\u2010induced intracranial osteosarcoma after radiation for acute lymphocytic leukemia associated with Li\u2010Fraumeni syndrome","volume":"41","author":"Yoshimura J","year":"2013","journal-title":"No Shinkei Geka"},{"key":"e_1_2_7_52_1","first-page":"22","article-title":"A case of early lung cancer detected by surveillance PET\/CT for Li\u2010Fraumeni syndrome","volume":"1","author":"Tanaka S","year":"2017","journal-title":"J Fam Tumor"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2016.02.031"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.5833\/jjgs.2015.0230"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000948"},{"key":"e_1_2_7_56_1","article-title":"ClinGen TP53 variant curation expert panel. Specifications of the ACMG\/AMP variant interpretation guidelines for germline TP53 variants","author":"Fortuno C","year":"2020","journal-title":"Hum Mutat"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1431692100"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0204-y"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23739"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.057570"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2007.10.044"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl132"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-10-0496"},{"key":"e_1_2_7_64_1","first-page":"6643","article-title":"Li\u2010Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype","volume":"63","author":"Olivier M","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0674-5"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12525"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-15-0578"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1086\/302575"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.1.02004"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2198"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23349"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199101000-00001"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.7112"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14919","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.14919","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14919","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T02:56:45Z","timestamp":1693191405000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.14919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":72,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1111\/cas.14919"],"URL":"https:\/\/doi.org\/10.1111\/cas.14919","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,17]]},"assertion":[{"value":"2020-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}