{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:02:11Z","timestamp":1792252931194,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,8,6]],"date-time":"2013-08-06T00:00:00Z","timestamp":1375747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>\n                      High\u2010grade serous ovarian cancer (\n                      <jats:styled-content style=\"fixed-case\">HGSC<\/jats:styled-content>\n                      ) is characterized by poor outcome, often attributed to the emergence of treatment\u2010resistant subclones. We sought to measure the degree of genomic diversity within primary, untreated\n                      <jats:styled-content style=\"fixed-case\">HGSCs<\/jats:styled-content>\n                      to examine the natural state of tumour evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on 31 spatially and temporally separated\n                      <jats:styled-content style=\"fixed-case\">HGSC<\/jats:styled-content>\n                      tumour specimens (six patients), including ovarian masses, distant metastases and fallopian tube lesions. We found widespread intratumoural variation in mutation, copy number and gene expression profiles, with key driver alterations in genes present in only a subset of samples (eg\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">PIK3CA<\/jats:styled-content>\n                      <\/jats:italic>\n                      ,\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">CTNNB1<\/jats:styled-content>\n                      <\/jats:italic>\n                      ,\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">NF1<\/jats:styled-content>\n                      <\/jats:italic>\n                      ). On average, only 51.5% of mutations were present in every sample of a given case (range 10.2\u201391.4%), with\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">TP53<\/jats:styled-content>\n                      <\/jats:italic>\n                      as the only somatic mutation consistently present in all samples. Complex segmental aneuploidies, such as whole\u2010genome doubling, were present in a subset of samples from the same individual, with divergent copy number changes segregating independently of point mutation acquisition. Reconstruction of evolutionary histories showed one patient with mixed\n                      <jats:styled-content style=\"fixed-case\">HGSC<\/jats:styled-content>\n                      and endometrioid histology, with common aetiologic origin in the fallopian tube and subsequent selection of different driver mutations in the histologically distinct samples. In this patient, we observed mixed cell populations in the early fallopian tube lesion, indicating that diversity arises at early stages of tumourigenesis. Our results revealed that\n                      <jats:styled-content style=\"fixed-case\">HGSCs<\/jats:styled-content>\n                      exhibit highly individual evolutionary trajectories and diverse genomic tapestries prior to therapy, exposing an essential biological characteristic to inform future design of personalized therapeutic solutions and investigation of drug\u2010resistance mechanisms. \u00a9 2013 The Authors. Journal of Pathology published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.\n                    <\/jats:bold>\n                  <\/jats:p>","DOI":"10.1002\/path.4230","type":"journal-article","created":{"date-parts":[[2013,6,18]],"date-time":"2013-06-18T12:21:17Z","timestamp":1371558077000},"page":"21-34","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":370,"title":["Distinct evolutionary trajectories of primary high\u2010grade serous ovarian cancers revealed through spatial mutational profiling"],"prefix":"10.1002","volume":"231","author":[{"given":"Ali","family":"Bashashati","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology British Columbia Cancer Agency Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology British Columbia 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