biostudies-literatureBenvenuti SAssociazione Italiana per la Ricerca sul CancroMinistero della SaluteTelethonAssociazione Italiana per la Ricerca sul Cancro (AIRC)FPRC 5x1000 2014 Ministero SaluteMinistero della Salute (Ministry of Health, Italy)e11756https://www.ebi.ac.uk/biostudies/studies/S-EPMC7338804biostudies-literatureUnknown12(7)Cancer of unknown primary (CUP) is an obscure disease characterized by multiple metastases in the absence of a primary tumor. No consensus has been reached whether CUPs are simply generated from cancers that cannot be detected or whether they are the manifestation of a still unknown nosological entity. Here, we report the complete expression and genetic analysis of multiple synchronous metastases harvested at warm autopsy of a patient with CUP. The expression profiles were remarkably similar and astonishingly singular. The whole exome analysis yielded a high number of mutations present in all metastases (fully shared), additional mutations (partially shared) accumulated one after another in a series, and few private mutations were unique to each metastasis. Surprisingly, the phylogenetic tEMBO molecular medicineCancer of Unknown Primary (CUP): genetic evidence for a novel nosological entity? A case report.PMC7338804TGM6S0121052Sapino AGambardella GComoglio PMMilan MGeuna EBoccaccio CBenvenuti SMontemurro FSenetta RStella GMPisacane AfalseCancer of Unknown Primary (CUP): genetic evidence for a novel nosological entity? A case report.Cancer of unknown primary (CUP) is an obscure disease characterized by multiple metastases in the absence of a primary tumor. No consensus has been reached whether CUPs are simply generated from cancers that cannot be detected or whether they are the manifestation of a still unknown nosological entity. Here, we report the complete expression and genetic analysis of multiple synchronous metastases harvested at warm autopsy of a patient with CUP. The expression profiles were remarkably similar and astonishingly singular. The whole exome analysis yielded a high number of mutations present in all metastases (fully shared), additional mutations (partially shared) accumulated one after another in a series, and few private mutations were unique to each metastasis. Surprisingly, the phylogenetic t2020-01-01T00:00:00Z2020 Jul2025-05-29T19:52:36.391Z2025-05-29T19:52:36.391ZS-EPMC73388043251186910.15252/emmm.201911756