{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:09:57Z","timestamp":1791202197091,"version":"4.2.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,11,8]],"date-time":"2001-11-08T00:00:00Z","timestamp":1005177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Checkpoint genes, activated in response to DNA damage and other stresses, are frequently targeted for alteration in cancer. Checkpoint kinase 2 (<jats:italic>CHK2, CDS1, RAD53<\/jats:italic>) is activated by ataxia telangiectasia mutated (ATM) in response to \u03b3 irradiation. Activated <jats:italic>CHK2<\/jats:italic> stabilizes TP53, and acts on other cell cycle and stress regulators. These findings place <jats:italic>CHK2<\/jats:italic> in the middle of a pathway frequently targeted in cancer. Because of this, and the observation that <jats:italic>CHK2<\/jats:italic> mutations are inherited in some Li\u2010Fraumeni cancer syndrome families, we decided to examine the role of <jats:italic>CHK2<\/jats:italic> mutations in sporadic cancers. Exploiting the genomic sequence of chromosome 22, we looked for mutations in the exons and intron junctions of the <jats:italic>CHK2<\/jats:italic> gene in DNA samples from 170 patients (57 osteosarcomas, 25 other sarcomas, 35 nonsmall\u2010cell lung, 20 ovarian, and 33 breast cancers). Missense mutations affecting the forkhead and kinase domains were detected in four osteosarcomas and in one ovarian and one lung cancer. These findings of <jats:italic>CHK2<\/jats:italic> gene mutations are consistent with osteosarcoma being a defining tumor of Li\u2010Fraumeni syndrome. The occurrence of <jats:italic>CHK2<\/jats:italic> mutations in sporadic cancers emphasizes the importance of the stress pathway which includes TP53.<\/jats:p>","DOI":"10.1002\/gcc.1207","type":"journal-article","created":{"date-parts":[[2002,9,9]],"date-time":"2002-09-09T19:37:26Z","timestamp":1031600246000},"page":"17-21","source":"Crossref","is-referenced-by-count":80,"title":["Mutations of the <i>CHK2<\/i> gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors"],"prefix":"10.1002","volume":"33","author":[{"given":"Carl W.","family":"Miller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ikezoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utz","family":"Krug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolf\u2010K.","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigal","family":"Tavor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaya","family":"Vegesna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiro","family":"Tsukasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seisho","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Phillip","family":"Koeffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,11,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5449.2528"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.99-1078rev"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.6.4262"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.3745"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202925"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1101\/gad.14.3.278","article-title":"CHK2\/hCds1 functions as a DNA damage checkpoint in G\u20101 by stabilizing TP53","volume":"14","author":"Chehab NH","year":"2000","journal-title":"Genes Dev"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/990031"},{"key":"e_1_2_6_9_1","first-page":"4689","article-title":"Absence of germline CHK2 mutations in familial gastric cancer","volume":"60","author":"Haruki N","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5459.1824"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(00)00130-2"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0888-7543(05)80277-0"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/PL00022979","article-title":"Mutation analysis of the hCHK2 gene in primary human malignant gliomas","volume":"3","author":"Ino Y","year":"2000","journal-title":"Neurogenetics"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2000.tb01028.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/095530099139359"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/35004614"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(96)66011-X"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5395.1893"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202179"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/35053094"},{"key":"e_1_2_6_21_1","first-page":"1695","article-title":"P53 mutation in human lung tumors","volume":"52","author":"Miller CW","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01213553"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.47.1.285"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5478.359a"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009727200"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.1996.0005"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.1207","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.1207","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T11:19:02Z","timestamp":1700306342000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.1207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,11,8]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,1]]}},"alternative-id":["10.1002\/gcc.1207"],"URL":"https:\/\/doi.org\/10.1002\/gcc.1207","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,11,8]]}}}