{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:23:53Z","timestamp":1791829433365,"version":"4.3.4"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research"},{"name":"PRIN program"},{"name":"Progetti di Ricerca di Rilevante Interesse Nazionale 2022","award":["Prot 20222KAYY5"],"award-info":[{"award-number":["Prot 20222KAYY5"]}]},{"name":"Associazione Italiana Ricerca sul Cancro AIRC","award":["IG2015-17691"],"award-info":[{"award-number":["IG2015-17691"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Adrenal cortical carcinoma (ACC) is a rare malignancy with a generally poor but heterogeneous prognosis, especially depending on the tumour stage at diagnosis. Identification of somatic gene alterations combined with clinical\/histopathological evaluation of the tumour can help improve prognostication. We applied a simplified targeted-Next-Generation Sequencing (NGS) panel to characterise the mutational profiles of ACCs, providing potentially relevant information for better patient management.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and methods<\/jats:title>\n                  <jats:p>Thirty frozen tumour specimens from a local ACC series were retrospectively analysed by a custom-NGS panel (CDKN2A, CTNNB1, DAXX, MED12, NF1, PRKAR1A, RB1, TERT, TP53, ZNRF3) to detect somatic prioritised single-nucleotide variants. This cohort was integrated with 86 patients from the ACC-TCGA series bearing point-mutations in the same genes and their combinations identified by our panel. Primary endpoints of the analysis on the total cohort (113 patients) were overall survival (OS) and progression-free survival (PFS), and hazard ratio (HR) for the different alterations grouped by the signalling pathways\/combinations affected.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Different PFS, OS, and HR were associated to the different pathways\/combinations, being NF1 + TP53 and Wnt\/\u03b2-catenin + Rb\/p53 combined mutations the most deleterious, with a statistical significance for progression HR which is retained only in low-(I\/II) stages\u2014NF1 + TP53 combination: HR = 2.96[1.01-8.69] and HR = 13.23[3.15-55.61], all and low stages, respectively; Wnt\/\u03b2-catenin + Rb\/p53 combined pathways: HR = 6.47[2.54-16.49] and HR = 16.24[3.87-68.00], all and low-stages, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A simplified targeted-NGS approach seems the best routinely applicable first step towards somatic genetic characterisation of ACC for prognostic assessment. This approach proved to be particularly promising in low-stage cases, suggesting the need for more stringent surveillance and personalised treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvae077","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T19:26:45Z","timestamp":1719343605000},"page":"17-30","source":"Crossref","is-referenced-by-count":9,"title":["Targeted Next Generation Sequencing molecular profiling and its clinical application in adrenocortical cancer"],"prefix":"10.1093","volume":"191","author":[{"given":"Francesca","family":"Cioppi","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy"},{"name":"European Network for the Study of Adrenal Tumours (ENSAT) Centre of Excellence, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Cantini","sequence":"additional","affiliation":[{"name":"European Network for the Study of Adrenal Tumours (ENSAT) Centre of Excellence, University of Florence, 50139 Florence, Italy"},{"name":"Department of Experimental and Clinical Biomedical Sciences, Endocrinology Section, University of Florence , 50139 Florence , Italy"},{"name":"Centro di Ricerca e Innovazione sulle Patologie Surrenaliche, AOU Careggi , 50139 Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonino","family":"Ercolino","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliero-Universitaria Careggi, (AOUC) , 50139 Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Chetta","sequence":"additional","affiliation":[{"name":"Medical Genetics, Azienda Ospedaliera di Rilievo Nazionale (A.O.R.N.) Cardarelli, Padiglione , 80131 Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Zanatta","sequence":"additional","affiliation":[{"name":"European Network for the Study of Adrenal Tumours (ENSAT) Centre of Excellence, University of Florence, 50139 Florence, Italy"},{"name":"Department of Experimental and Clinical Biomedical Sciences, Endocrinology Section, University of Florence , 50139 Florence , Italy"},{"name":"Azienda Ospedaliero-Universitaria Careggi, (AOUC) , 50139 Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Nesi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Florence , 50139 Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Mannelli","sequence":"additional","affiliation":[{"name":"European Network for the Study of Adrenal Tumours (ENSAT) Centre of Excellence, University of Florence, 50139 Florence, Italy"},{"name":"Department of Experimental and Clinical Biomedical Sciences, Endocrinology Section, University of Florence , 50139 Florence , Italy"},{"name":"Centro di Ricerca e Innovazione sulle Patologie Surrenaliche, AOU Careggi , 50139 Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Maggi","sequence":"additional","affiliation":[{"name":"European Network for the Study of Adrenal Tumours (ENSAT) Centre of Excellence, University of Florence, 50139 Florence, Italy"},{"name":"Department of Experimental and Clinical Biomedical Sciences, Endocrinology Section, University of Florence , 50139 Florence , Italy"},{"name":"Centro di Ricerca e Innovazione sulle Patologie Surrenaliche, AOU Careggi , 50139 Florence , Italy"},{"name":"Azienda Ospedaliero-Universitaria Careggi, (AOUC) , 50139 Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4995-8108","authenticated-orcid":false,"given":"Letizia","family":"Canu","sequence":"additional","affiliation":[{"name":"European Network for the Study of Adrenal Tumours (ENSAT) Centre of Excellence, University of Florence, 50139 Florence, Italy"},{"name":"Department of Experimental and Clinical Biomedical Sciences, Endocrinology Section, University of Florence , 50139 Florence , Italy"},{"name":"Centro di Ricerca e Innovazione sulle Patologie Surrenaliche, AOU Careggi , 50139 Florence , Italy"},{"name":"Azienda Ospedaliero-Universitaria Careggi, (AOUC) , 50139 Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5186-064X","authenticated-orcid":false,"given":"Michaela","family":"Luconi","sequence":"additional","affiliation":[{"name":"European Network for the Study of Adrenal Tumours (ENSAT) Centre of Excellence, University 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