{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:57:58Z","timestamp":1791356278144,"version":"4.3.1"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2006,9,25]],"date-time":"2006-09-25T00:00:00Z","timestamp":1159142400000},"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; Cancer"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in <jats:italic>ATM<\/jats:italic> are responsible for the autosomal recessive disorder ataxia telangiectasia. Heterozygous mutations in <jats:italic>ATM<\/jats:italic> have been associated with an elevated risk of breast cancer. We previously reported one breast cancer family in which <jats:italic>ATM<\/jats:italic> 7271T&gt;G (V2424G) segregated with disease, and apparently acted in a dominant negative manner. We now report the screening of 782 multiple\u2010case breast cancer families that identified two additional index cases with <jats:italic>ATM<\/jats:italic> 7271T&gt;G. Phylogenetic sequence analysis showed that V2424 is a highly conserved residue, and that the 2424G variant is likely to interfere with function. To elucidate the consequences of this mutation, we expression profiled wild\u2010type, heterozygous, and homozygous lymphoblastoid cell lines (LCLs) from Scottish and Australian families using an oligonucleotide microarray. Cluster analysis revealed 77 genes that were differentially expressed in homozygous and heterozygous V2424G cells (compared to wild\u2010type) and 11 genes differentially expressed in the homozygous cells. We also evaluated the profiles of LCLs after exposure to ionizing radiation (IR) and identified 77 genes that were differentially expressed in wild\u2010type cells, but not in homozygous or heterozygous V2424G cells. We validated the expression differences by RT\u2010PCR in additional heterozygous V2424G LCLs from another breast cancer family. We found no consistent cytotoxicity or abrogation of ATM kinase activity after IR in seven heterozygous V2424G LCLs, compared to wild\u2010type LCLs, but did find an increase in the number of chromosomal aberrations. These data suggest that the V2424G missense mutation acts largely as a dominant negative in terms of the associated expression profiles. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20381","type":"journal-article","created":{"date-parts":[[2006,9,25]],"date-time":"2006-09-25T16:01:58Z","timestamp":1159200118000},"page":"1169-1181","source":"Crossref","is-referenced-by-count":18,"title":["Characterization of the breast cancer associated <i>ATM<\/i> 7271T&gt;G (V2424G) mutation by gene expression 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