{"entity": "publication", "iuid": "afbdbc4e56d745e5828ca00b03ae2e10", "timestamp": "2026-11-09T14:37:08.434Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/afbdbc4e56d745e5828ca00b03ae2e10.json"}, "display": {"href": "https://publications.scilifelab.se/publication/afbdbc4e56d745e5828ca00b03ae2e10"}}, "title": "Genomic Catastrophe Defines the Evolutionary Trajectory of Adrenocortical Carcinoma.", "authors": [{"family": "Backman", "given": "Samuel", "initials": "S"}, {"family": "Axling", "given": "Fredrik", "initials": "F"}, {"family": "Zhang", "given": "Liang", "initials": "L"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Juhlin", "given": "C Christofer", "initials": "CC"}, {"family": "Barazeghi", "given": "Elham", "initials": "E"}, {"family": "Skogseid", "given": "Britt", "initials": "B"}, {"family": "Klim\u00e1cek", "given": "Branislav", "initials": "B"}, {"family": "Anneb\u00e4ck", "given": "Matilda", "initials": "M"}, {"family": "Zedenius", "given": "Jan", "initials": "J"}, {"family": "Norl\u00e9n", "given": "Olov", "initials": "O"}, {"family": "St\u00e5lberg", "given": "Peter", "initials": "P"}, {"family": "Crona", "given": "Joakim", "initials": "J"}, {"family": "\u00c5kerstr\u00f6m", "given": "Tobias", "initials": "T"}], "type": "journal article", "published": "2026-06-10", "journal": {"title": "Endocr. Pathol.", "issn": "1559-0097", "volume": "37", "issue": "1", "issn-l": "1046-3976"}, "abstract": "The mechanisms underlying how adrenocortical carcinoma (ACC) progresses into a metastatic and lethal disease remain poorly understood. To address this, we performed comprehensive genomic analyses to delineate the evolutionary trajectory of advanced ACC. Fresh frozen tumour samples (n = 29) were obtained from nine patients, all of whom had matched primary and relapse specimens, including recurrent (n = 4) and metastatic (n = 11) 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.", "doi": "10.1007/s12022-026-09922-2", "pmid": "42265438", "labels": {"National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service", "NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13249746"}, {"db": "pii", "key": "10.1007/s12022-026-09922-2"}], "notes": [], "created": "2026-11-06T09:09:58.230Z", "modified": "2026-11-06T09:09:58.239Z"}