{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T21:48:22Z","timestamp":1776203302868,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,5]],"date-time":"2022-06-05T00:00:00Z","timestamp":1654387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["5X1000, funds 2015-2016"],"award-info":[{"award-number":["5X1000, funds 2015-2016"]}]},{"name":"Italian Ministry of Health","award":["20760"],"award-info":[{"award-number":["20760"]}]},{"name":"IRCCS Ospedale Policlinico San Martino, AIRC IG2017","award":["5X1000, funds 2015-2016"],"award-info":[{"award-number":["5X1000, funds 2015-2016"]}]},{"name":"IRCCS Ospedale Policlinico San Martino, AIRC IG2017","award":["20760"],"award-info":[{"award-number":["20760"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The study of circulating cancer-derived components (circulome) is considered the new frontier of liquid biopsy. Despite the recognized role of circulome biomarkers, their comparative molecular profiling is not yet routine. In advanced breast cancer (BC), approximately 40% of hormone-receptor-positive, HER2-negative BC cases harbor druggable PIK3CA mutations suitable for combined alpelisib\/fulvestrant treatment. This pilot study investigates PIK3CA mutations in circulating tumor DNA (ctDNA), tumor cells (CTCs), and extracellular vesicles (EVs) with the aim of determining which information on molecular targetable profiling could be recollected in each of them. The in-depth molecular analysis of four BC patients demonstrated, as a proof-of-concept study, that it is possible to retrieve mutational information in the three components. Patient-specific PIK3CA mutations were found in both tissue and ctDNA and in 3\/4 cases, as well as in CTCs, in the classical population (large-sized CD45\u2212\/EpCAM+\/\u2212 cells), and\/or in the \u201cnon-conventional\u201d sub-population (smaller-sized CD44+\/EpCAM\u2212\/CD45\u2212 cells). Consistent mutational profiles of EVs with CTCs suggest that they may have been released by CTCs. This preliminary evidence on the molecular content of the different circulating biomaterials suggests their possible function as a mirror of the intrinsic heterogeneity of BC. Moreover, this study demonstrates, through mutational assessment, the tumor origin of the different CTC sub-populations sustaining the translational value of the circulome for a more comprehensive picture of the disease.<\/jats:p>","DOI":"10.3390\/ijms23116320","type":"journal-article","created":{"date-parts":[[2022,6,5]],"date-time":"2022-06-05T10:47:11Z","timestamp":1654426031000},"page":"6320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Targeting PIK3CA Actionable Mutations in the Circulome: A Proof of Concept in Metastatic Breast Cancer"],"prefix":"10.3390","volume":"23","author":[{"given":"Barbara","family":"Cardinali","sequence":"first","affiliation":[{"name":"Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppa","family":"De Luca","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Unit, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Tasso","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genova, 5-16126 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5296-4325","authenticated-orcid":false,"given":"Simona","family":"Coco","sequence":"additional","affiliation":[{"name":"Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Garuti","sequence":"additional","affiliation":[{"name":"Clinica Oncologia Medica ad Indirizzo Oncologico, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Buzzatti","sequence":"additional","affiliation":[{"name":"Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Sciutto","sequence":"additional","affiliation":[{"name":"Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3818-0364","authenticated-orcid":false,"given":"Luca","family":"Arecco","sequence":"additional","affiliation":[{"name":"Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6853-2359","authenticated-orcid":false,"given":"Federico","family":"Villa","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franca","family":"Carli","sequence":"additional","affiliation":[{"name":"Surgical Pathology Unit, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Reverberi","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1146-894X","authenticated-orcid":false,"given":"Rodolfo","family":"Quarto","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genova, 5-16126 Genova, Italy"},{"name":"Cellular Oncology Unit, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-0278","authenticated-orcid":false,"given":"Mariella","family":"Dono","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Unit, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9546-5841","authenticated-orcid":false,"given":"Lucia","family":"Del Mastro","sequence":"additional","affiliation":[{"name":"Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 10-16132 Genova, Italy"},{"name":"Department of Internal Medicine and Medical Specialties (DIMI), University of Genova, 5-16126 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1515\/cclm-2020-1685","article-title":"Updates on liquid biopsy: Current trends and future perspectives for clinical application in solid tumors","volume":"59","author":"Pinzani","year":"2021","journal-title":"Clin. 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