{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:34:59Z","timestamp":1789457699134,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,6,2]],"date-time":"2004-06-02T00:00:00Z","timestamp":1086134400000},"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":[[2004,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Breast cancer risk is greatly increased in women who carry mutations in the <jats:italic>BRCA1<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic> genes. Because breast cancer initiation is different between <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> mutation carriers and women who do not carry mutations, it is possible that the mechanism of breast cancer progression is also different. Histopathologic and genetic studies have supported this hypothesis. To test this hypothesis further, we utilized a large cohort of women who underwent therapeutic mastectomy (TM) and contralateral prophylactic mastectomy (PM). From this cohort, we developed case groups of women with a family history of breast cancer with <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> deleterious mutations, with unclassified variant alterations, and with no detected mutation and matched these cases with sporadic controls from the same TM and PM cohort. Fluorescence in situ hybridization was performed on paraffin sections by use of dual\u2010color probes for <jats:italic>ERBB2<\/jats:italic>\/<jats:italic>CEP17<\/jats:italic>, <jats:italic>MYC<\/jats:italic>\/<jats:italic>CEP8<\/jats:italic>, <jats:italic>TBX2<\/jats:italic>\/<jats:italic>CEP17<\/jats:italic>, and <jats:italic>RPS6KB1<\/jats:italic>\/<jats:italic>CEP17<\/jats:italic>. All malignant and benign lesions, including putative precursor lesions, were studied. The invasive cancers from deleterious mutation carriers had a higher prevalence of duplication of <jats:italic>MYC<\/jats:italic> (<jats:italic>P<\/jats:italic> = 0.006) and <jats:italic>TBX2<\/jats:italic> (<jats:italic>P<\/jats:italic> = 0.0008) compared to controls and a lower prevalence of <jats:italic>ERBB2<\/jats:italic> amplification (<jats:italic>P<\/jats:italic> = 0.011). Coduplication of <jats:italic>MYC<\/jats:italic> and <jats:italic>TBX2<\/jats:italic> was common in the in situ and invasive lesions from the deleterious mutation carriers. The odds ratio of having a <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> mutation is 31.4 (95% CI = 1.7\u2013569) when <jats:italic>MYC<\/jats:italic> and <jats:italic>TBX2<\/jats:italic> are coduplicated but <jats:italic>ERBB2<\/jats:italic> is normal. Unclassified variant carriers\/no mutation detected and sporadic controls had a similar prevalence of alterations, suggesting that hereditary patients with no deleterious mutations follow a progression pathway similar to that of sporadic cases. With the exception of one atypical ductal hyperplasia lesion, no putative precursor lesion showed any detectable alteration of the probes tested. There was no significant intratumoral heterogeneity of genetic alterations. Our data confirm that a specific pattern of genomic instability characterizes <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic>\u2010related cancers and that this pattern has implications for the biology of these cancers. Moreover, our current and previous results emphasize the interaction between phenotype and genotype in <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic>\u2010related breast cancers and that a combination of morphologic features and alterations of <jats:italic>ERBB2, MYC<\/jats:italic>, and <jats:italic>TBX2<\/jats:italic> may better define mechanisms of tumor progression, as well as determine which patients are more likely to carry <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> mutations. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20057","type":"journal-article","created":{"date-parts":[[2004,6,2]],"date-time":"2004-06-02T22:00:52Z","timestamp":1086213652000},"page":"1-11","source":"Crossref","is-referenced-by-count":44,"title":["<i>ERBB2<\/i>, <i>TBX2<\/i>, <i>RPS6KB1<\/i>, and <i>MYC<\/i> alterations in breast tissues of <i>BRCA1<\/i> and <i>BRCA2<\/i> mutation carriers"],"prefix":"10.1002","volume":"41","author":[{"given":"Camilo","family":"Adem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl L.","family":"Soderberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Hafner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Slezak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen S.","family":"Sinclair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Sellers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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