{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:42:15Z","timestamp":1772757735373,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,9,5]],"date-time":"2006-09-05T00:00:00Z","timestamp":1157414400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract:\u2002<\/jats:sc><\/jats:bold>  <jats:bold>Breast cancer recurrence is a result of undetected metastasis present at the time of primary patient treatment. More sensitive methods are needed to identify subclinical disease progression to better accompany those increasing advances in early breast cancer screening. Aberrant hypermethylation of tumor\u2010suppressor genes is found frequently in primary breast tumors and has been implicated in disease initiation and progression. Epigenetic characterization of tumor cells may provide highly specific and sensitive molecular surrogates for surveillance. We evaluated whether tumor\u2010associated methylated DNA markers could be identified circulating in bone marrow (BM) aspirates and paired serum samples from 33 early\u2010stage patients undergoing surgery for breast cancer. Quantitative methylation\u2010specific PCR (qMSP) was performed using a selected tumor\u2010related gene panel for RAR\u2010\u00df2, MGMT, RASSF1A, and APC. Tumor\u2010associated hypermethylated DNA was identified in 7 (21%) of 33 BM aspirates and 9 (27%) serum samples. In three patients both BM and serum were positive for hypermethylation. The most frequently detected hypermethylation marker was RASSF1A occurring in 7 (21%) patients. Concordance was present between gene hypermethylation detected in BM or serum samples, and matched\u2010pair primary tumors. Advanced AJCC stage was associated with an increased incidence of circulating gene hypermethylation. In addition, methylation patterns in the sentinel lymph node (SLN) metastasis corresponded with that of the primary tumor, confirming epigenetic clonality is associated with early tumor dissemination. This study demonstrates the novel finding of tumor\u2010associated epigenetic markers in BM aspirates\/blood and their potential role as targets for molecular detection.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1368.029","type":"journal-article","created":{"date-parts":[[2006,11,16]],"date-time":"2006-11-16T03:12:04Z","timestamp":1163646724000},"page":"211-221","source":"Crossref","is-referenced-by-count":34,"title":["Epigenetic Analysis of Body Fluids and Tumor Tissues"],"prefix":"10.1111","volume":"1075","author":[{"given":"BRET","family":"TABACK","sequence":"first","affiliation":[]},{"given":"ARMANDO E.","family":"GIULIANO","sequence":"additional","affiliation":[]},{"given":"RON","family":"LAI","sequence":"additional","affiliation":[]},{"given":"NORA","family":"HANSEN","sequence":"additional","affiliation":[]},{"given":"FREDERICK R.","family":"SINGER","sequence":"additional","affiliation":[]},{"given":"KLAUS","family":"PANTEL","sequence":"additional","affiliation":[]},{"given":"DAVE S.B.","family":"HOON","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2006,9,5]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198902233200802"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1989.7.3.355"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1988.6.1.89"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19910215)67:4<1033::AID-CNCR2820670428>3.0.CO;2-H"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200002243420801"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5340.1054"},{"key":"e_1_2_6_8_2","first-page":"3251","article-title":"Presence of tumor DNA in plasma of breast cancer patients: clinicopathological correlations","volume":"59","author":"Silva J.M.","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb03860.x"},{"key":"e_1_2_6_10_2","first-page":"3761","article-title":"Tumor DNA in plasma at diagnosis of breast cancer patients is a valuable predictor of disease\u2010free survival","volume":"8","author":"Silva J.M.","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"e_1_2_6_11_2","first-page":"3899","article-title":"Quantitative analysis of aberrant p16 methylation using real\u2010time quantitative methylation\u2010specific polymerase chain reaction","volume":"59","author":"Lo Y.M.","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_6_12_2","first-page":"3225","article-title":"A gene hypermethylation profile of human cancer","volume":"61","author":"Esteller M.","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_6_13_2","first-page":"7641","article-title":"DNA methylation in serum of breast cancer patients: an independent prognostic marker","volume":"63","author":"Muller H.M.","year":"2003","journal-title":"Cancer Res."},{"key":"e_1_2_6_14_2","first-page":"1884","article-title":"Detection of tumor\u2010specific genetic alterations in bone marrow from early\u2010stage breast cancer patients","volume":"63","author":"Taback B.","year":"2003","journal-title":"Cancer Res."},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207505"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64880-8"},{"key":"e_1_2_6_17_2","first-page":"3105","article-title":"Hypermethylation of the cpG island of Ras association domain family 1A (RASSF1A), a putative tumor suppressor gene from the 3p21.3 locus, occurs in a large percentage of human breast cancers","volume":"61","author":"Dammann R.","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2001.1853"},{"key":"e_1_2_6_19_2","first-page":"4346","article-title":"Aberrant methylation of the estrogen receptor and E\u2010cadherin 5\u2032 CpG islands increases with malignant progression in human breast cancer","volume":"60","author":"Nass S.J.","year":"2000","journal-title":"Cancer Res."},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9821"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.10.826"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205606"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0118"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)04501-3"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-0410-3"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1318.005"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1196%2Fannals.1368.029","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1196\/annals.1368.029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T04:01:35Z","timestamp":1695614495000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1196\/annals.1368.029"}},"subtitle":["Application of a Comprehensive Molecular Assessment for Early\u2010Stage Breast Cancer Patients"],"short-title":[],"issued":{"date-parts":[[2006,9]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,9]]}},"alternative-id":["10.1196\/annals.1368.029"],"URL":"https:\/\/doi.org\/10.1196\/annals.1368.029","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9]]}}}