{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:51:37Z","timestamp":1791910297595,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000301","name":"Breast Cancer Campaign","doi-asserted-by":"publisher","award":["2011MaySF01"],"award-info":[{"award-number":["2011MaySF01"]}],"id":[{"id":"10.13039\/501100000301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005973","name":"Dr. Mildred Scheel Stiftung f\u00fcr Krebsforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005973","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006386","name":"Adenoid Cystic Carcinoma Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006386","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA008748"],"award-info":[{"award-number":["P30CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000869","name":"Susan G. Komen for the Cure","doi-asserted-by":"publisher","award":["PDF14298348"],"award-info":[{"award-number":["PDF14298348"]}],"id":[{"id":"10.13039\/100000869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale","doi-asserted-by":"publisher","award":["Interface"],"award-info":[{"award-number":["Interface"]}],"id":[{"id":"10.13039\/501100001677","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":[[2015,10]]},"abstract":"Abstract<\/jats:title>Adenoid cystic carcinoma (AdCC<\/jats:styled-content>) is a rare type of triple\u2010negative breast cancer (TNBC<\/jats:styled-content>) characterized by the presence of the MYB\u2013NFIB<\/jats:styled-content><\/jats:italic> fusion gene. The molecular underpinning of breast AdCCs<\/jats:styled-content> other than the MYB\u2013NFIB<\/jats:styled-content><\/jats:italic> fusion gene remains largely unexplored. Here we sought to define the repertoire of somatic genetic alterations of breast AdCCs<\/jats:styled-content>. We performed whole\u2010exome sequencing, followed by orthogonal validation, of 12 breast AdCCs<\/jats:styled-content> to determine the landscape of somatic mutations and gene copy number alterations. Fluorescence in situ<\/jats:italic> hybridization and reverse\u2010transcription PCR<\/jats:styled-content> were used to define the presence of MYB<\/jats:styled-content><\/jats:italic> gene rearrangements and MYB\u2013NFIB<\/jats:styled-content><\/jats:italic> chimeric transcripts. Unlike common forms of TNBC<\/jats:styled-content>, we found that AdCCs<\/jats:styled-content> have a low mutation rate (0.27 non\u2010silent mutations\/Mb), lack mutations in TP53<\/jats:styled-content><\/jats:italic> and PIK3CA<\/jats:styled-content><\/jats:italic> and display a heterogeneous constellation of known cancer genes affected by somatic mutations, including MYB<\/jats:styled-content><\/jats:italic>, BRAF<\/jats:styled-content><\/jats:italic>, FBXW7<\/jats:styled-content><\/jats:italic>, SMARCA5<\/jats:styled-content><\/jats:italic>, SF3B1<\/jats:styled-content><\/jats:italic> and FGFR2<\/jats:styled-content>. MYB<\/jats:styled-content><\/jats:italic> and TLN2<\/jats:styled-content><\/jats:italic> were affected by somatic mutations in two cases each. Akin to salivary gland AdCCs<\/jats:styled-content>, breast AdCCs<\/jats:styled-content> were found to harbour mutations targeting chromatin remodelling, cell adhesion, RNA<\/jats:styled-content> biology, ubiquitination and canonical signalling pathway genes. We observed that, although breast AdCCs<\/jats:styled-content> had rather simple genomes, they likely display intra\u2010tumour genetic heterogeneity at diagnosis. Taken together, these findings demonstrate that the mutational burden and mutational repertoire of breast AdCCs<\/jats:styled-content> are more similar to those of salivary gland AdCCs<\/jats:styled-content> than to those of other types of TNBCs<\/jats:styled-content>, emphasizing the importance of histological subtyping of TNBCs<\/jats:styled-content>. Furthermore, our data provide direct evidence that AdCCs<\/jats:styled-content> harbour a distinctive mutational landscape and genomic structure, irrespective of the disease site of origin. Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4573","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T19:49:31Z","timestamp":1434743371000},"page":"179-189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":149,"title":["Genomic landscape of adenoid cystic carcinoma of the breast"],"prefix":"10.1002","volume":"237","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9625-1183","authenticated-orcid":false,"given":"Luciano G","family":"Martelotto","sequence":"first","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R","family":"De Filippo","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte KY","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Natrajan","sequence":"additional","affiliation":[{"name":"Breakthrough Breast Cancer Research Centre The Institute of Cancer Research London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Fuhrmann","sequence":"additional","affiliation":[{"name":"Department of Tumour Biology Institut Curie Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Cyrta","sequence":"additional","affiliation":[{"name":"Department of Tumour Biology Institut Curie Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Piscuoglio","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei\u2010Chi","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond S","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronglai","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M","family":"Schultheis","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y Hannah","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia","family":"Edelweiss","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odette","family":"Mariani","sequence":"additional","affiliation":[{"name":"Department of Tumour Biology Institut Curie Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"Stenman","sequence":"additional","affiliation":[{"name":"Sahlgrenska Cancer Center, Department of Pathology University of Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A","family":"Chan","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre\u2010Emmanuel","family":"Colombo","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology Montpellier Cancer Institute (ICM) France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Norton","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Vincent\u2010Salomon","sequence":"additional","affiliation":[{"name":"Department of Tumour Biology Institut Curie Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge S","family":"Reis\u2010Filho","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Weigelt","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2009.073908"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2407"},{"key":"e_1_2_7_4_1","volume-title":"WHO Classification of Tumours of the Breast","author":"Lakhani SR","year":"2012"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2009.166"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1001389"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp245"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21458"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909114106"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.86"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3182002777"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-0463"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2643"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67201"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2974"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12050"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2014.07.013"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.21965"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10933"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11412"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-013-2740-6"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1991.tb00229.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2014.06.011"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.6529"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.50.9984"},{"key":"e_1_2_7_26_1","article-title":"Resolving quandaries: basaloid adenoid cystic carcinoma or breast cylindroma? The role of massively parallel sequencing","author":"Fusco N","year":"2015","journal-title":"Histopathology"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2909"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3096"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2514"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.129684.111"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts271"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3069"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbs017"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0810-575"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1133"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0484-1"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1055"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-4-r41"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2203"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12213"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1299"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12634"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12912"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.489"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.neo.7900158"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0915"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113205"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1253462"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12477"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.4573","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.4573","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.4573","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:24:11Z","timestamp":1760959451000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.4573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,14]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1002\/path.4573"],"URL":"https:\/\/doi.org\/10.1002\/path.4573","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,14]]},"assertion":[{"value":"2015-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-07-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}