{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:01:33Z","timestamp":1777003293305,"version":"3.51.4"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T00:00:00Z","timestamp":1580688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15H01834"],"award-info":[{"award-number":["15H01834"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ionizing radiation can damage DNA and, therefore, is a risk factor for cancer. Eker rats, which carry a heterozygous germline mutation in the tumor\u2010suppressor gene tuberous sclerosis complex 2 (<jats:italic>Tsc2<\/jats:italic>), are susceptible to radiation\u2010induced renal carcinogenesis. However, the molecular mechanisms involved in <jats:italic>Tsc2<\/jats:italic> inactivation are unclear. We subjected Fischer 344\u00a0\u00d7\u00a0Eker (Long Evans <jats:italic>Tsc2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>) F1 hybrid rats to gamma\u2010irradiation (2\u00a0Gy) at gestational day 19 (GD19) or postnatal day 5 (PND5) and investigated the patterns of genomic alterations in the <jats:italic>Tsc2<\/jats:italic> allele of renal tumors that developed at 1\u00a0year after irradiation (N\u00a0=\u00a024 tumors for GD19, N\u00a0=\u00a010 for PND5), in comparison with spontaneously developed tumors (N\u00a0=\u00a08 tumors). Gamma\u2010irradiation significantly increased the multiplicity of renal tumors. The frequency of LOH at the chromosome 10q12 region, including the <jats:italic>Tsc2<\/jats:italic> locus, was 38%, 29% and 60% in renal carcinomas developed from the nonirradiated, GD19 and PND5 groups, respectively. Array comparative genomic hybridization analysis revealed that the LOH patterns on chromosome 10 in renal carcinomas were classified into chromosomal missegregation, mitotic recombination and chromosomal deletion types. LOH of the interstitial chromosomal deletion type was observed only in radiation\u2010associated carcinomas. Sequence analysis for the wild\u2010type Tsc2 allele in the LOH\u2010negative carcinomas identified deletions (nonirradiated: 26%; GD19: 21%) and base\u2010substitution mutations (GD19: 4%). Reduced expression of Tsc2 was also observed in the majority of the LOH\u2010negative carcinomas. Our results suggest that interstitial chromosomal deletion is a characteristic mutagenic event caused by ionizing radiation, and it may contribute to the assessment of radiation\u2010induced cancer risk.<\/jats:p>","DOI":"10.1111\/cas.14307","type":"journal-article","created":{"date-parts":[[2020,1,11]],"date-time":"2020-01-11T10:45:09Z","timestamp":1578739509000},"page":"840-848","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Interstitial chromosomal deletion of the tuberous sclerosis complex 2 locus is a signature for radiation\u2010associated renal tumors in Eker rats"],"prefix":"10.1111","volume":"111","author":[{"given":"Tatsuya","family":"Inoue","sequence":"first","affiliation":[{"name":"Department of Radiation Effects Research National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology Chiba Japan"},{"name":"Department of Radiology Juntendo University 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Technology Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takamitsu","family":"Morioka","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shino","family":"Homma\u2010Takeda","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences for Radiation Damages National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Oncology Faculty of Medicine Juntendo University Tokyo 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