{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:09:57Z","timestamp":1790078997865,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","award":["6\u20102022\u20100168"],"award-info":[{"award-number":["6\u20102022\u20100168"]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","award":["6\u20102024\u20100153"],"award-info":[{"award-number":["6\u20102024\u20100153"]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lynch syndrome (LS) is a hereditary cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes, most notably associated with colorectal cancer. Although LS patients face high risk of CRC, risk can vary even among those with the same pathogenic MMR germline mutations. We suggest a functional assay platform for assessing mutation risk using patient\u2010derived organoid (PDOs). We measured organoid response to the cytotoxic effects of a methylating agent,\n                    <jats:italic>N<\/jats:italic>\n                    \u2010methyl\u2010\n                    <jats:italic>N\u2032<\/jats:italic>\n                    \u2010nitro\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010nitrosoguanidine (MNNG) based on DNA damage\u2010induced apoptosis. When normal (non\u2010LS) colon organoids were used, treatment with MNNG and four passages of organoid culture led to decreased total growth (organoid area), but there was no significant change in number. To increase the effect of MNNG and induce apoptosis in normal colon organoids, we added O\n                    <jats:sup>6<\/jats:sup>\n                    BG (an MGMT inhibitor) and an ATR inhibitor. The cytotoxic effects of combined treatment with MNNG, O\n                    <jats:sup>6<\/jats:sup>\n                    BG and ATR inhibitor on non\u2010LS\u2010PDOs were significantly higher than in PDOs of LS patients. To detect the difference at an earlier phase, we examined DNA damage response by analyzing \u03b3H2AX expression after treatment with MNNG and O6BG for 24\u2009h. Then, we found higher expression of \u03b3H2AX in non\u2010LS\u2010PDOs than in PDOs of LS patients, suggesting continued cell survival with mutation accumulation in LS\u2010PDOs. In conclusion, treatment with MNNG and O6BG using PDOs and measurement of resulting DNA damage response could be used as a preclinical platform for risk stratification in LS patients.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70646","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T03:00:37Z","timestamp":1783738837000},"page":"2585-2594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Mutation Risk Using Patient\u2010Derived Organoids in Patients With Lynch Syndrome"],"prefix":"10.1002","volume":"159","author":[{"given":"Youmi","family":"Shin","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine and Institute of Gastroenterology, Severance Hospital Yonsei University College of Medicine  Seoul Korea"},{"name":"Graduate School of Medical Science, Brain Korea 21 Project Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Keon","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine and Institute of Gastroenterology, Severance Hospital Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoojeong","family":"Seo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine and Institute of Gastroenterology, Severance Hospital Yonsei University College of Medicine  Seoul Korea"},{"name":"Graduate School of Medical Science, Brain Korea 21 Project Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine and Institute of Gastroenterology, Severance Hospital Yonsei University College of Medicine  Seoul Korea"},{"name":"Department of Medicine Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihye","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine and Institute of Gastroenterology, Severance Hospital Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Jung","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine and Institute of Gastroenterology, Severance Hospital Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Jun","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine and Institute of Gastroenterology, Severance Hospital Yonsei University College of Medicine  Seoul Korea"},{"name":"Yonsei Cancer Prevention Center Severance Hospital, Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hee","family":"Cheon","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine and Institute of Gastroenterology, Severance Hospital Yonsei University College of Medicine  Seoul Korea"},{"name":"Graduate School of Medical Science, Brain Korea 21 Project Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongwon","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Seoul Clinical Laboratories  Yongin\u2010si Gyeonggi\u2010do Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanghoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Companion Biomarker Center Seoul Clinical Laboratories Healthcare Inc  Yongin\u2010si Gyeonggi\u2010do Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4807-890X","authenticated-orcid":false,"given":"Tae Il","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine and Institute of Gastroenterology, Severance Hospital Yonsei University College of Medicine  Seoul Korea"},{"name":"Graduate School of Medical Science, Brain Korea 21 Project Yonsei University College of Medicine  Seoul Korea"},{"name":"Yonsei Cancer Prevention Center Severance Hospital, Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21601"},{"key":"e_1_2_14_3_1","first-page":"9","article-title":"The Molecular Characteristics of Colorectal Cancer: Implications for Diagnosis and Therapy","volume":"16","author":"Nguyen H. T.","year":"2018","journal-title":"Oncology Letters"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.12.064"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22262"},{"key":"e_1_2_14_6_1","volume-title":"StatPearls","author":"Bhattacharya P.","year":"2025"},{"key":"e_1_2_14_7_1","volume-title":"StatPearls","author":"Bhattacharya P.","year":"2021"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.5217\/ir.2023.00112"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.32604\/or.2025.063951"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2024.0062"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.35106"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118767"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/narcan\/zcad031"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021808"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2024.102226"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2024.0408"},{"key":"e_1_2_14_17_1","unstructured":"The Jamovi Project \u201cJamovi (Version 2.7) [Computer Software] \u201d2026."},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.06.006"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20056"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152008784220276"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1996.485"},{"key":"e_1_2_14_22_1","first-page":"837","article-title":"O6\u2010Benzylguanine and Its Role in Chemotherapy","volume":"3","author":"Dolan M. E.","year":"1997","journal-title":"Clinical Cancer Research"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.5.1803"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1004"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2ib20091k"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.120"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.294404"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v9.i9.2073"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.001"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15912-7"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/22.12.1931"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2007.115"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.03.071"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao3130"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2021.103178"},{"key":"e_1_2_14_36_1","first-page":"1351","article-title":"Patient\u2010Derived Organoids in Precision Cancer Medicine","volume":"5","author":"Tong L.","year":"2024","journal-title":"Medicus"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.11.029"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70646","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.70646","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70646","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:32:20Z","timestamp":1790076740000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70646"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,11,15]]}},"alternative-id":["10.1002\/ijc.70646"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70646","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]},"assertion":[{"value":"2025-12-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}