{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:55:55Z","timestamp":1776682555483,"version":"3.51.2"},"reference-count":29,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2021,8,6]]},"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Gene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Cell lines harbouring <jats:italic>EML4<\/jats:italic>(13)<jats:italic>\u2013ALK<\/jats:italic>(20) and <jats:italic>SLC34A2<\/jats:italic>(4)<jats:italic>\u2013ROS1<\/jats:italic>(32) gene fusions were adopted to prepare reference standards. Eight laboratories (five adopting amplicon-based and three hybridisation-based platforms) received, at different dilution points two sets of slides (slide A 50.0%, slide B 25.0%, slide C 12.5% and slide D wild type) stained by Papanicolaou (Pap) and May Grunwald Giemsa (MGG). Analysis was carried out on a total of 64 slides.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Four (50.0%) out of eight laboratories reported results on all slides and dilution points. While 12 (37.5%) out of 32 MGG slides were inadequate, 27 (84.4%) out of 32 Pap slides produced libraries adequate for variant calling. The laboratories using hybridisation-based platforms showed the highest rate of inadequate results (13\/24 slides, 54.2%). Conversely, only 10.0% (4\/40 slides) of inadequate results were reported by laboratories adopting amplicon-based platforms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Reference standards in cytological format yield better results when Pap staining and processed by amplicon-based assays. Further investigation is required to optimise these standards for MGG stained cells and for hybridisation-based approaches.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jclinpath-2021-207825","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T13:39:11Z","timestamp":1629812351000},"page":"47-52","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Reference standards for gene fusion molecular assays on cytological samples: an international validation study"],"prefix":"10.1136","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3211-9957","authenticated-orcid":false,"given":"Umberto","family":"Malapelle","sequence":"first","affiliation":[{"name":"Public Health, University of Naples Federico II, Naples, Italy"}]},{"given":"Francesco","family":"Pepe","sequence":"additional","affiliation":[{"name":"Public Health, University of Naples Federico II, Naples, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-0620","authenticated-orcid":false,"given":"Pasquale","family":"Pisapia","sequence":"additional","affiliation":[{"name":"Public Health, University of Naples Federico II, Naples, Italy"}]},{"given":"Annalisa","family":"Altimari","sequence":"additional","affiliation":[{"name":"Molecular Pathology, University of Bologna Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Bologna, Italy"}]},{"given":"Claudio","family":"Bellevicine","sequence":"additional","affiliation":[{"name":"Public Health, University of Naples Federico II, Naples, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7402-138X","authenticated-orcid":false,"given":"Hans","family":"Brunnstr\u00f6m","sequence":"additional","affiliation":[{"name":"Clinical Sciences Lund, Division of Pathology, Lund University, Lund, Sweden"}]},{"given":"Rossella","family":"Bruno","sequence":"additional","affiliation":[{"name":"Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy"}]},{"given":"Reinhard","family":"B\u00fcttner","sequence":"additional","affiliation":[{"name":"Pathology, University of Cologne, Koln, Germany"}]},{"given":"Luis","family":"Cirnes","sequence":"additional","affiliation":[{"name":"Pathology, IPATIMUP, Porto, Portugal"}]},{"given":"Carlos E","family":"De Andrea","sequence":"additional","affiliation":[{"name":"Pathology, University of Navarra, Pamplona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0609-8817","authenticated-orcid":false,"given":"Dario","family":"de Biase","sequence":"additional","affiliation":[{"name":"Pharmacy and Biotechnology (FaBiT), Molecular Pathology Laboratory, University of Bologna, Bologna, Italy"}]},{"given":"Catherine I","family":"Dumur","sequence":"additional","affiliation":[{"name":"Aurora Diagnostics, Jacksonville, Florida, USA"}]},{"given":"Kajsa","family":"Ericson Lindquist","sequence":"additional","affiliation":[{"name":"Clinical Sciences Lund, Division of Pathology, 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