{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:52:43Z","timestamp":1792450363932,"version":"4.5.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Young Scientists","award":["20K18207"],"award-info":[{"award-number":["20K18207"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["20K09636"],"award-info":[{"award-number":["20K09636"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["19K16572"],"award-info":[{"award-number":["19K16572"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["22K09563"],"award-info":[{"award-number":["22K09563"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["20H03695"],"award-info":[{"award-number":["20H03695"]}]},{"name":"Grant-in-Aid for Challenging Research Pioneering","award":["25K21788"],"award-info":[{"award-number":["25K21788"]}]},{"name":"BRIDGE"},{"name":"National Cancer Center Research and Development Fund","award":["2023-J"],"award-info":[{"award-number":["2023-J"]}]},{"name":"NCC Biobank"},{"name":"NCC Core Facility"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Human papillomavirus infection contributes to the development of almost all cervical malignancies, aside from gastric-type adenocarcinoma of the cervix, a rare aggressive subtype without human papillomavirus infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To address the carcinogenic mechanism of this disease, we performed a comparative multi-omics analysis of gastric-type adenocarcinoma of the cervix and usual-type endocervical adenocarcinoma in 3 independent cohorts of patients with gastric-type adenocarcinoma of the cervix and usual-type endocervical adenocarcinoma. The first cohort comprised 8 gastric-type adenocarcinoma of the cervix and 22 patients with usual-type endocervical adenocarcinoma treated at the National Cancer Center Hospital between 2002 and 2020, who were examined by targeted and whole transcriptome sequencing. The other 2 cohorts comprised 52 patients with gastric-type adenocarcinoma of the cervix and 109 patients with usual-type endocervical adenocarcinoma and 39 patients with gastric-type adenocarcinoma of the cervix and 232 patients with usual-type endocervical adenocarcinoma, whose mutational data were obtained from the Center for Cancer Genomics and Advanced Therapeutics (Japanese patients) and Genomics Evidence Neoplasia Information Exchange (US patients) public databases, respectively. Metabolomic analysis was performed in 8 patients, including 5 with gastric-type adenocarcinoma of the cervix.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>TP53 mutations were more prevalent in gastric-type adenocarcinoma of the cervix than in usual-type endocervical adenocarcinoma in all 3 cohorts. Transcriptome analysis consistently revealed frequent suppression of TP53-related pathways in gastric-type adenocarcinoma of the cervix. Metabolites preferentially detected in gastric-type adenocarcinoma of the cervix tissues suggest TP53 alterations are implicated in intratumoral metabolic properties.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The development of gastric-type adenocarcinoma of the cervix is likely driven by TP53 mutations, which play a large role in shaping intracellular signaling and metabolic profiles within tumor cells.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jncics\/pkaf082","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T11:36:19Z","timestamp":1754393779000},"source":"Crossref","is-referenced-by-count":6,"title":["<i>TP53<\/i> gene and pathway alterations in gastric-type adenocarcinoma of the cervix"],"prefix":"10.1093","volume":"9","author":[{"given":"Daiki","family":"Higuchi","sequence":"first","affiliation":[{"name":"Division of Genome Biology, National Cancer Center Research Institute , Tokyo,","place":["Japan"]},{"name":"Department of Obstetrics and Gynecology, Showa Medical University , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiko","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Division of Genome Biology, National Cancer Center Research Institute , Tokyo,","place":["Japan"]},{"name":"Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0782-0922","authenticated-orcid":false,"given":"Erisa","family":"Fujii","sequence":"additional","affiliation":[{"name":"Division of Genome Biology, National Cancer Center Research Institute , Tokyo,","place":["Japan"]},{"name":"Department of Gynecology, National Cancer Center Hospital , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4065-0289","authenticated-orcid":false,"given":"Mayumi Kobayashi","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Genome Biology, National Cancer Center Research Institute , Tokyo,","place":["Japan"]},{"name":"Department of Gynecology, National Cancer Center Hospital , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Hiranuma","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2047-5618","authenticated-orcid":false,"given":"Yuka","family":"Asami","sequence":"additional","affiliation":[{"name":"Division of Genome Biology, National Cancer Center Research Institute , 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Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6184-618X","authenticated-orcid":false,"given":"Koji","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Showa Medical University , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2249-1333","authenticated-orcid":false,"given":"Akihiko","family":"Sekizawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Showa Medical University , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8855-2966","authenticated-orcid":false,"given":"Mitsuya","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Gynecology, National Cancer Center Hospital , 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