{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:16:44Z","timestamp":1790162204974,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,5,7]],"date-time":"2015-05-07T00:00:00Z","timestamp":1430956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AIRC Foundation","award":["MFAG10570"],"award-info":[{"award-number":["MFAG10570"]}]},{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation (BCRF)","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Brussels Region"},{"name":"CARIGE Foundation"},{"name":"ESMO Translational Research Fellowship"},{"name":"Fonds Lambeau-Marteaux"},{"name":"Fonds National de la Recherche Scientifique (FNRS)"},{"name":"Les Amis de l'Institut Bordet"},{"name":"San Paolo Foundation"},{"name":"Wellcome Trust Clinical Research Training Fellowhip Programs"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2015,8]]},"abstract":"Abstract<\/jats:title>\n \n Multifocal breast cancer (\n MFBC<\/jats:styled-content>\n ), defined as multiple synchronous unilateral lesions of invasive breast cancer, is relatively frequent and has been associated with more aggressive features than unifocal cancer. Here, we aimed to investigate the genomic heterogeneity between\n MFBC<\/jats:styled-content>\n lesions sharing similar histopathological parameters. Characterization of different lesions from 36 patients with ductal\n MFBC<\/jats:styled-content>\n involved the identification of non\u2010silent coding mutations in 360 protein\u2010coding genes (171 tumour and 36 matched normal samples). We selected only patients with lesions presenting the same grade,\n ER<\/jats:styled-content>\n , and\n HER2<\/jats:styled-content>\n status. Mutations were classified as \u2018oncogenic\u2019 in the case of recurrent substitutions reported in\n COSMIC<\/jats:styled-content>\n or truncating mutations affecting tumour suppressor genes. All mutations identified in a given patient were further interrogated in all samples from that patient through deep resequencing using an orthogonal platform. Whole\u2010genome rearrangement screen was further conducted in 8\/36 patients. Twenty\u2010four patients (67%) had substitutions\/indels shared by all their lesions, of which 11 carried the same mutations in all lesions, and 13 had lesions with both common and private mutations. Three\u2010quarters of those 24 patients shared oncogenic variants. The remaining 12 patients (33%) did not share any substitution\/indels, with inter\u2010lesion heterogeneity observed for oncogenic mutation(s) in genes such as\n \n PIK3CA<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n TP53<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n GATA3<\/jats:styled-content>\n <\/jats:italic>\n , and\n \n PTEN<\/jats:styled-content>\n <\/jats:italic>\n . Genomically heterogeneous lesions tended to be further apart in the mammary gland than homogeneous lesions. Genome\u2010wide analyses of a limited number of patients identified a common somatic background in all studied\n MFBCs<\/jats:styled-content>\n , including those with no mutation in common between the lesions. To conclude, as the number of molecular targeted therapies increases and trials driven by genomic screening are ongoing, our findings highlight the presence of genomic inter\u2010lesion heterogeneity in one\u2010third, despite similar pathological features. This implies that deeper molecular characterization of all\n MFBC<\/jats:styled-content>\n lesions is warranted for the adequate management of those cancers. \u00a9 2015 The Authors. Pathological Society of Great Britain and Ireland.\n <\/jats:p>","DOI":"10.1002\/path.4540","type":"journal-article","created":{"date-parts":[[2015,4,6]],"date-time":"2015-04-06T09:13:55Z","timestamp":1428311635000},"page":"457-466","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Uncovering the genomic heterogeneity of multifocal breast cancer"],"prefix":"10.1002","volume":"236","author":[{"given":"Christine","family":"Desmedt","sequence":"first","affiliation":[{"name":"Breast Cancer Translational Research Laboratory Universit\u00e9 Libre de Bruxelles, Institut Jules Bordet Boulevard de Waterloo 121 Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"Breast Cancer Translational Research Laboratory Universit\u00e9 Libre de Bruxelles, Institut Jules Bordet Boulevard de Waterloo 121 Brussels 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