{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:32:37Z","timestamp":1784759557192,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Malignant tumours of the lacrimal apparatus are rare and frequently show a poor prognosis, with no clear therapeutic standards. Characterisation of the genetic landscape of these rare tumours is sparse, and therefore therapeutics generally follow those of their common salivary gland counterparts. To further clarify the pathophysiology and discover potential therapeutic targets, we investigated the genetic landscape of eight tumours of the lacrimal apparatus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>DNA and RNA sequencing were performed to identify genetic mutations and gene fusions. Immunohistochemistry, fluorescence <jats:italic>in\u2010situ<\/jats:italic> hybridisation and reverse transcription\u2013polymerase chain reaction followed by Sanger sequencing were performed to confirm the identified molecular alterations. Genetic alterations were detected in six tumours. Among five adenoid cystic carcinomas (ACC), four had confirmed alterations of <jats:italic>MYB<\/jats:italic> or <jats:italic>MYBL1<\/jats:italic> genes, including a <jats:italic>MYB<\/jats:italic>::<jats:italic>NFIB<\/jats:italic> fusion, a <jats:italic>MYBL1<\/jats:italic>::<jats:italic>NFIB<\/jats:italic> fusion, a <jats:italic>MYB<\/jats:italic> amplification and a novel <jats:italic>NFIB<\/jats:italic>::<jats:italic>THSD7B<\/jats:italic> fusion. Mutations in genes encoding epigenetic modifiers, as well as <jats:italic>NOTCH1<\/jats:italic>, <jats:italic>FGFR2<\/jats:italic> and <jats:italic>ATM<\/jats:italic> mutations, were also identified in ACCs. A carcinoma ex pleomorphic adenoma showed <jats:italic>TP53<\/jats:italic> and <jats:italic>CIC<\/jats:italic> mutations and an amplification of <jats:italic>ERBB2<\/jats:italic>. A transitional cell carcinoma was associated with HPV16 infection. No genetic alteration was found for one adenocarcinoma, not otherwise specified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study highlights the variety of molecular alterations associated with lacrimal system tumours and emphasises the importance of molecular testing in these tumours, which can reveal potentially targetable mutations. Our results also reinforce the hypothesis of a common physiopathology of all ACCs, regardless of their primary location.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15040","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T15:56:24Z","timestamp":1694706984000},"page":"925-935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular characterisation of tumours of the lacrimal apparatus"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5202-0212","authenticated-orcid":false,"given":"Roseline","family":"Vibert","sequence":"first","affiliation":[{"name":"Pharmacogenomics Unit, Department of Genetics Institut Curie, PSL Research University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Cyrta","sequence":"additional","affiliation":[{"name":"Department of Pathology Institut Curie, PSL Research University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Girard","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Systems Biology of Cancer PSL Research University, Mines Paris Tech, INSERM U900  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Vacher","sequence":"additional","affiliation":[{"name":"Pharmacogenomics Unit, Department of Genetics Institut Curie, PSL Research University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9lia","family":"Dupain","sequence":"additional","affiliation":[{"name":"Department of Drug Development and Innovation (D3i) Institut Curie  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Antonio","sequence":"additional","affiliation":[{"name":"Pharmacogenomics Unit, Department of Genetics Institut Curie, PSL Research University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Wong","sequence":"additional","affiliation":[{"name":"Pharmacogenomics Unit, Department of Genetics Institut Curie, PSL Research University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Baulande","sequence":"additional","affiliation":[{"name":"Institut Curie Genomics of Excellence (ICGex) NGS Platform Institut Curie  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Monteiro Ferras","family":"De Sousa","sequence":"additional","affiliation":[{"name":"Department of Pathology Institut Curie, PSL Research University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5754-5771","authenticated-orcid":false,"given":"Anne","family":"Vincent\u2010Salomon","sequence":"additional","affiliation":[{"name":"Department of Pathology Institut Curie, PSL Research University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Masliah\u2010Planchon","sequence":"additional","affiliation":[{"name":"Pharmacogenomics Unit, Department of Genetics Institut Curie, PSL Research University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girard","sequence":"additional","affiliation":[{"name":"Thorax Institute Curie Montsouris Institut Curie  Paris France"},{"name":"UVSQ Paris Saclay University  Versailles France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Le Tourneau","sequence":"additional","affiliation":[{"name":"Department of Drug Development and Innovation (D3i) Institut Curie  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Kamal","sequence":"additional","affiliation":[{"name":"Department of Drug Development and Innovation (D3i) Institut Curie  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Bi\u00e8che","sequence":"additional","affiliation":[{"name":"Pharmacogenomics Unit, Department of Genetics Institut Curie, PSL Research University  Paris France"},{"name":"Faculty of Pharmaceutical and Biological Sciences, INSERM U1016 Universit\u00e9 de Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,14]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"WHO classification of tumours of the eye: WHO classification of tumours","author":"Grossniklaus HE","year":"2018"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2009.209"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/01676830.2020.1769684"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2008.12.049"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1722700"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-0859"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67201"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2643"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000945"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2016.307"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2013.03.030"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41389-021-00309-y"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0005-y"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5006"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.86"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1870"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2867-T"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.020"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.01.013"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI128227"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467212666190215112915"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0425-3"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-022-01001-y"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.5264"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2018.59.6.717"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/aos.13310"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0637"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy269.149"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.2007.00893.x"},{"key":"e_1_2_8_31_1","first-page":"284","article-title":"HPV may not play a role in all lacrimal transitional cell papilloma","volume":"51","author":"Jones H","year":"2020","journal-title":"Rhinology"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.5858\/133.8.1268"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.15040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T07:26:29Z","timestamp":1699255589000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.15040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,14]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1111\/his.15040"],"URL":"https:\/\/doi.org\/10.1111\/his.15040","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,14]]},"assertion":[{"value":"2023-04-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}