{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:02:49Z","timestamp":1789599769944,"version":"build-2803163510"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Genet"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The BRCA2 and MRE11 proteins participate in the repair of double-strand DNA breaks by homologous recombination. Germline <jats:italic>BRCA2<\/jats:italic> mutations predispose to ovarian, breast and pancreatic cancer, while a germline <jats:italic>MRE11<\/jats:italic> mutation is associated with an ataxia telangiectasia-like disorder. Somatic mutations of <jats:italic>BRCA2<\/jats:italic> are rare in typical sporadic cancers. In tumors having microsatellite instability (MSI), somatic truncating mutations in a poly [A] tract of <jats:italic>BRCA2<\/jats:italic> are reported on occasion.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We analyzed gastrointestinal MSI cancers by whole gene <jats:italic>BRCA2<\/jats:italic> sequencing, finding heterozygous truncating mutations in seven (47%) of 15 patients. There was no cellular functional defect in RAD51 focus-formation in three heterozygously mutated lines studied, although other potential functions of the BRCA2 protein could still be affected. A prior report of mutations in primary MSI tumors affecting the IVS5-(5\u201315) poly [T] tract of the <jats:italic>MRE11<\/jats:italic> gene was confirmed and extended by analysis of the genomic sequence and protein expression in MSI cancer cell lines. Statistical analysis of the published <jats:italic>MRE11<\/jats:italic> mutation rate in MSI tumors did not provide evidence for a selective pressure favoring biallelic mutations at this repeat.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Perhaps conflicting with common suspicions, the data are not compatible with selective pressures during tumorigenesis promoting the functional loss of <jats:italic>BRCA2<\/jats:italic> and <jats:italic>MRE11<\/jats:italic> in MSI tumors. Instead, these data fit closely with an absence of selective pressures acting on <jats:italic>BRCA2<\/jats:italic> and <jats:italic>MRE11<\/jats:italic> gene status during tumorigenesis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2156-7-3","type":"journal-article","created":{"date-parts":[[2006,1,23]],"date-time":"2006-01-23T13:04:26Z","timestamp":1138021466000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Does tumorigenesis select for or against mutations of the DNA repair-associated genes BRCA2 and MRE11?: Considerations from somatic mutations in microsatellite unstable (MSI) gastrointestinal cancers"],"prefix":"10.1186","volume":"7","author":[{"given":"Michiel S","family":"van der Heijden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R","family":"Brody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elhaam","family":"Elghalbzouri-Maghrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata Z","family":"Zdzienicka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E","family":"Kern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,1,17]]},"reference":[{"key":"426_CR1","first-page":"5548","volume":"55","author":"R Parsons","year":"1995","unstructured":"Parsons R, Myeroff LL, Liu B, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B: Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer. 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