{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:59:07Z","timestamp":1761101947038},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,10,27]],"date-time":"2010-10-27T00:00:00Z","timestamp":1288137600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Only a few studies have addressed the molecular pathways specifically involved in carcinogenesis of the distal colon and rectum. We aimed to identify potential differences among genetic alterations in distal colon and rectal carcinomas as compared to cancers arising elsewhere in the large bowel.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Constitutional and tumor DNA from a test series of 37 patients with rectal and 25 patients with sigmoid carcinomas, previously analyzed for microsatellite instability (MSI), was studied for <jats:italic>BAX<\/jats:italic>, <jats:italic>IGF2R<\/jats:italic>, <jats:italic>TGFBR2<\/jats:italic>, <jats:italic>MSH3<\/jats:italic>, and <jats:italic>MSH6<\/jats:italic> microsatellite sequence alterations, <jats:italic>BRAF<\/jats:italic> and <jats:italic>KRAS<\/jats:italic> mutations, and <jats:italic>MLH1<\/jats:italic> promoter methylation. The findings were then compared with those of an independent validation series consisting of 36 MSI-H carcinomas with origin from each of the large bowel regions. Immunohistochemical and germline mutation analyses of the mismatch repair system were performed when appropriate.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In the test series, <jats:italic>IGFR2<\/jats:italic> and <jats:italic>BAX<\/jats:italic> mutations were present in one and two out of the six distal MSI-H carcinomas, respectively, and no mutations were detected in <jats:italic>TGFBR2<\/jats:italic>, <jats:italic>MSH3<\/jats:italic>, and <jats:italic>MSH6<\/jats:italic>. We confirmed these findings in the validation series, with <jats:italic>TGFBR2<\/jats:italic> and <jats:italic>MSH3<\/jats:italic> microsatellite mutations occurring less frequently in MSI-H rectal and sigmoid carcinomas than in MSI-H colon carcinomas elsewhere (<jats:italic>P<\/jats:italic> = 0.00005 and <jats:italic>P<\/jats:italic> = 0.0000005, respectively, when considering all MSI-carcinomas of both series). No <jats:italic>MLH1<\/jats:italic> promoter methylation was observed in the MSI-H rectal and sigmoid carcinomas of both series, as compared to 53% found in MSI-H carcinomas from other locations (<jats:italic>P<\/jats:italic> = 0.004). <jats:italic>KRAS<\/jats:italic> and <jats:italic>BRAF<\/jats:italic> mutational frequencies were 19% and 43% in proximal carcinomas and 25% and 17% in rectal\/sigmoid carcinomas, respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The mechanism and the pattern of genetic changes driving MSI-H carcinogenesis in distal colon and rectum appears to differ from that occurring elsewhere in the colon and further investigation is warranted both in patients with sporadic or hereditary disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-10-587","type":"journal-article","created":{"date-parts":[[2010,11,11]],"date-time":"2010-11-11T19:16:05Z","timestamp":1289502965000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Colorectal carcinomas with microsatellite instability display a different pattern of target gene mutations according to large bowel site of origin"],"prefix":"10.1186","volume":"10","author":[{"given":"Manuela","family":"Pinheiro","sequence":"first","affiliation":[]},{"given":"Terje","family":"Ahlquist","sequence":"additional","affiliation":[]},{"given":"Stine A","family":"Danielsen","sequence":"additional","affiliation":[]},{"given":"Guro E","family":"Lind","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Veiga","sequence":"additional","affiliation":[]},{"given":"Carla","family":"Pinto","sequence":"additional","affiliation":[]},{"given":"Vera","family":"Costa","sequence":"additional","affiliation":[]},{"given":"Lu\u00eds","family":"Afonso","sequence":"additional","affiliation":[]},{"given":"Olga","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"Maria","family":"Fragoso","sequence":"additional","affiliation":[]},{"given":"L\u00facio","family":"Santos","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[]},{"given":"Paula","family":"Lopes","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Lopes","sequence":"additional","affiliation":[]},{"given":"Ragnhild A","family":"Lothe","sequence":"additional","affiliation":[]},{"given":"Manuel R","family":"Teixeira","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,10,27]]},"reference":[{"key":"2386_CR1","volume-title":"IARC CancerBase n\u00b05, version 2.0","author":"J Ferlay","year":"2004","unstructured":"Ferlay J, Bray F, Pisani P, Parkin DM: GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide. 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