{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T07:45:39Z","timestamp":1765525539516,"version":"3.48.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A23464"],"award-info":[{"award-number":["A23464"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Formalin\u2010fixed paraffin\u2010embedded (FFPE) tissue specimens represent precious resources for clinical genomic profiling studies, especially when coupled with comprehensive medical records. Even though next\u2010generation sequencing (NGS) is an effective tool to detect somatic mutations and somatic copy number alterations (sCNA), the biggest challenges in unlocking clinically translatable genomic information from FFPE tissue are low DNA yields and degraded DNA, affected by variable formalin fixation. Another issue is that the proportion of carcinoma and other noncarcinoma cells is variable and can be confounded by intratumoral heterogeneity. To explore these challenges, we isolated pure carcinoma and stromal cells using the DEPArray\u2122 NxT system, a microchip\u2010based digital sorter that allows isolation of pure, homogeneous subpopulations of cells from FFPE samples. We isolated pure carcinoma and stromal cell populations from 12 FFPE tissues, including tissues from nine primary and metastatic breast cancer and three primary ovarian high\u2010grade serous carcinomas. This was followed by downstream shallow whole\u2010genome sequencing (WGS) for copy number landscape profiling (10 samples) and\/or a targeted panel for somatic mutation and sCNA analysis (seven samples), subject to cell availability. Seven out of 10 samples (even some with low tumour content or of old age) produced good\u2010quality genomic data, detecting sCNA in all carcinoma population samples but not in the stromal populations. Mutation analysis was performed successfully in 6\/7 samples and somatic mutations were detected in all of them. Our workflow enabled the identification of clinically actionable targets, including\n                    <jats:italic>PIK3CA, ERBB2, FGFR1\/2, CDK6, CCNE1, KRAS<\/jats:italic>\n                    amplifications and\n                    <jats:italic>RB, BRCA1\/2<\/jats:italic>\n                    losses in patients that would direct therapy. \u00a9 2025 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6469","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T04:27:03Z","timestamp":1761625623000},"page":"13-26","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of actionable targets using\n                    <scp>DEPArray<\/scp>\n                    \u2010based sorting of pure carcinoma and stromal populations from formalin\u2010fixed paraffin\u2010embedded tissues followed by shallow whole\u2010genome sequencing"],"prefix":"10.1002","volume":"268","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9764-4288","authenticated-orcid":false,"given":"Georgios","family":"Nteliopoulos","sequence":"first","affiliation":[{"name":"Department of Surgery and Cancer Imperial College London, Hammersmith Hospital Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3361-0274","authenticated-orcid":false,"given":"Evie","family":"Wren","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer Imperial College London, Hammersmith Hospital Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amelia","family":"Rushton","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer Imperial College London, Hammersmith Hospital Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc K","family":"Wadsley","sequence":"additional","affiliation":[{"name":"Leicester Cancer Research Centre, Department of Genetics, Genomics and Cancer Sciences University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4438-9666","authenticated-orcid":false,"given":"Daniel","family":"Fernandez\u2010Garcia","sequence":"additional","affiliation":[{"name":"Leicester Cancer Research Centre, Department of Genetics, Genomics and Cancer Sciences University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7387-9453","authenticated-orcid":false,"given":"Floriana","family":"Manodoro","sequence":"additional","affiliation":[{"name":"Genomics Facility (former TPU), Next\u2010generation Sequencing lab Brookes Lawley Building, Institute of Cancer Research  Sutton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0963-8129","authenticated-orcid":false,"given":"Otis","family":"Agbaimoni","sequence":"additional","affiliation":[{"name":"Genomics Facility (former TPU), Next\u2010generation Sequencing lab Brookes Lawley Building, Institute of Cancer Research  Sutton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ritika","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Genomics Facility (former TPU), Next\u2010generation Sequencing lab Brookes Lawley Building, Institute of Cancer Research  Sutton 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Building, Leicester Royal Infirmary  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4887-8632","authenticated-orcid":false,"given":"Rebecca C","family":"Allsopp","sequence":"additional","affiliation":[{"name":"Leicester Cancer Research Centre, Department of Genetics, Genomics and Cancer Sciences University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Bautista","sequence":"additional","affiliation":[{"name":"Menarini Silicon Biosystems SpA Via Giuseppe di Vittorio, Castel Maggiore  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-2113","authenticated-orcid":false,"given":"Ignazio","family":"Puccio","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer Imperial College London, Hammersmith Hospital Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0602-1131","authenticated-orcid":false,"given":"Nik","family":"Matthews","sequence":"additional","affiliation":[{"name":"Genomics Facility (former TPU), Next\u2010generation Sequencing lab Brookes Lawley Building, Institute of Cancer Research  Sutton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly LT","family":"Gleason","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer Imperial College London, Hammersmith Hospital Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3879-315X","authenticated-orcid":false,"given":"Rehman","family":"Farah","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Imperial College Healthcare NHS Trust, Charing Cross Hospital  London 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