{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T18:26:36Z","timestamp":1760984796761},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,3,22]],"date-time":"2013-03-22T00:00:00Z","timestamp":1363910400000},"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":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Ovarian carcinoma is a common, and often deadly, gynecological cancer. Mutations in <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> genes are present in at least a fifth of patients. Uncovering other genes that become mutated subsequent to <jats:italic>BRCA1\/BRCA2<\/jats:italic> inactivation during cancer development will be helpful for more effective treatments.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We performed exome sequencing on the blood, primary tumor, omental metastasis and recurrence following therapy with carboplatin and paclitaxel<jats:italic>,<\/jats:italic>\u2009from a patient carrying a\u2009<jats:italic>BRCA1<\/jats:italic>\u2009S1841R mutation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We observed loss of heterozygosity in the <jats:italic>BRCA1<\/jats:italic> mutation in the primary and subsequent tumors, and somatic mutations in the <jats:italic>TP53<\/jats:italic> and <jats:italic>NF1<\/jats:italic> genes were identified, suggesting their role along with <jats:italic>BRCA1<\/jats:italic> driving the tumor development. Notably, we show that exome sequencing is effective in detecting large chromosomal rearrangements such as deletions and amplifications in cancer. We found that a large deletion was present in the three tumors in the regions containing <jats:italic>BRCA1<\/jats:italic>, <jats:italic>TP53<\/jats:italic>, and <jats:italic>NF1<\/jats:italic> mutations, and an amplification in the regions containing <jats:italic>MYC<\/jats:italic>. We did not observe the emergence of any new mutations among tumors from diagnosis to relapse after chemotherapy, suggesting that mutations already present in the primary tumor contributed to metastases and chemotherapy resistance.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our findings suggest that exome sequencing of matched samples from one patient is a powerful method of detecting somatic mutations and prioritizing their potential role in the development of the disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-13-146","type":"journal-article","created":{"date-parts":[[2013,3,22]],"date-time":"2013-03-22T19:14:30Z","timestamp":1363979670000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Exome profiling of primary, metastatic and recurrent ovarian carcinomas in a BRCA1-positive patient"],"prefix":"10.1186","volume":"13","author":[{"given":"Jian","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilie","family":"Lalonde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Cavallone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Ferenczy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter H","family":"Gotlieb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William D","family":"Foulkes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacek","family":"Majewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,3,22]]},"reference":[{"issue":"9","key":"3765_CR1","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1038\/ng.893","volume":"43","author":"C Loveday","year":"2011","unstructured":"Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark E, Frankum JR, Bowden G, Kalmyrzaev B, Warren-Perry M, Snape K, Adlard JW, Barwell J, Berg J, Brady AF, Brewer C, Brice G, Chapman C, Cook J, Davidson R, Donaldson A, Douglas F, Greenhalgh L, Henderson A, Izatt L, Kumar A, Lalloo F, Miedzybrodzka Z, Morrison PJ, Paterson J, Porteous M, Rogers MT, Shanley S, Walker L, Eccles D, Evans DG, Renwick A, Seal S, Lord CJ, Ashworth A, Reis-Filho J, Antoniou AC, Rahman N: Germline mutations in RAD51D confer susceptibility to ovarian cancer. 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