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To address this, we performed comprehensive genomic analyses to delineate the evolutionary trajectory of advanced ACC. Fresh frozen tumour samples (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200929) were obtained from nine patients, all of whom had matched primary and relapse specimens, including recurrent (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094) and metastatic (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200911) lesions. In four patients, multiple primary and metastatic samples were available, enabling detailed evolutionary comparisons. All tumours underwent whole-genome sequencing, RNA sequencing, and DNA methylation profiling. Our analyses revealed that seven of nine patients exhibited global loss of heterozygosity (LOH) often followed by whole-genome doubling, resulting in copy-neutral LOH. SNP-based analyses indicated that these alterations occurred as a single catastrophic event that was conserved across all matched samples within each patient, suggesting that this event constitutes a truncal feature of the evolutionary tree. These results support a model in which chromosomal aneuploidy is important in ACC tumourigenesis, potentially distinguishing carcinomas from benign adrenal adenomas. This may explain the rarity of adenoma-to-carcinoma transformation and suggest a diagnostic and therapeutic relevance of chromosomal instability in ACC.\n                  <\/jats:p>","DOI":"10.1007\/s12022-026-09922-2","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T02:13:09Z","timestamp":1781057589000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic Catastrophe Defines the Evolutionary Trajectory of Adrenocortical Carcinoma"],"prefix":"10.1007","volume":"37","author":[{"given":"Samuel","family":"Backman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Axling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Botling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Christofer","family":"Juhlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Barazeghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt","family":"Skogseid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branislav","family":"Klim\u00e1cek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilda","family":"Anneb\u00e4ck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Zedenius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olov","family":"Norl\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"St\u00e5lberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joakim","family":"Crona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"\u00c5kerstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"issue":"2","key":"9922_CR1","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1210\/er.2013-1029","volume":"35","author":"T Else","year":"2014","unstructured":"Else T, Kim AC, Sabolch A, Raymond VM, Kandathil A, Caoili EM, et al. 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