{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:57:38Z","timestamp":1791320258098,"version":"4.3.1"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,1,25]],"date-time":"2013-01-25T00:00:00Z","timestamp":1359072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2013,2]]},"abstract":"Abstract<\/jats:title>\n \n \n PARP<\/jats:styled-content>\n inhibitors (\n PARPi<\/jats:styled-content>\n ) for the treatment of\n \n BRCA1<\/jats:styled-content>\n <\/jats:italic>\n or\n \n BRCA2<\/jats:styled-content>\n <\/jats:italic>\n deficient tumours are currently the focus of seminal clinical trials exploiting the concept of synthetic lethality. Although clinical resistance to\n PARPi<\/jats:styled-content>\n has been described, the mechanism underlying this has not been elucidated. Here, we investigate tumour material from patients who had developed resistance to the\n PARPi<\/jats:styled-content>\n olaparib, subsequent to showing an initial clinical response. Massively parallel\n DNA<\/jats:styled-content>\n sequencing of treatment\u2010naive and post\u2010olaparib treatment biopsies identified tumour\u2010specific\n \n BRCA2<\/jats:styled-content>\n <\/jats:italic>\n secondary mutations in olaparib\u2010resistant metastases. These secondary mutations restored full\u2010length\n BRCA2<\/jats:styled-content>\n protein, and most likely cause olaparib resistance by re\u2010establishing\n BRCA2<\/jats:styled-content>\n function in the tumour cells. Copyright \u00a9 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:bold>\n <\/jats:p>","DOI":"10.1002\/path.4140","type":"journal-article","created":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T04:47:40Z","timestamp":1353386860000},"page":"422-429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":309,"title":["Secondary mutations in\n \n BRCA2<\/scp>\n <\/i>\n associated with clinical resistance to a\n PARP<\/scp>\n inhibitor"],"prefix":"10.1002","volume":"229","author":[{"given":"Louise J","family":"Barber","sequence":"first","affiliation":[{"name":"Breakthrough Breast Cancer Research Centre Institute of Cancer Research London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahneen","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Royal Marsden NHS Foundation Trust and Institute of Cancer Research Sutton Surrey 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