Title : Genomic signatures of mucinous ovarian tumours with mural nodules: Distinguishing features from mucinous tumours without mural nodules and dedifferentiated mucinous carcinoma
Abstract:
Aim: To investigate the molecular events underlying Mucinous ovarian Tumours with Mural Nodules (MTMN) and compare them with mucinous tumours without mural nodules, with attention to differential diagnosis against Dedifferentiated Mucinous Carcinoma (DDMC).
Methods: Targeted genomic profiling was performed on 47 cases, including 12 MTMN and 35 mucinous tumours without mural nodules (22 carcinomas, 10 borderline tumours, 3 cystadenomas). One DDMC was analysed for comparison.
Results: Early oncogenic events were identified in cystadenomas, with KRAS mutations in 67%, CDKN2A in 33%, and PIK3CA in 33%. With progression, mutational burden increased, peaking in mucinous carcinomas (KRAS 86%, TP53 81%, CDKN2A 58%, ERBB2 42%). MTMN showed clonal origin between mucinous and mural components, with shared KRAS (92%) and TP53 (92%), but divergence where ARID1 and DNMT3A were present in epithelial but absent in mural nodules. Novel events in MTMN included TERT, MAP2K1, MED12, and SOX17. DDMC was distinct, with triple impairment of DNA repair/chromatin remodeling (BRCA2, SMARCA4, ARID1A), never observed in MTMN.
Conclusions: Molecular events begin early in mucinous tumorigenesis, accumulate with progression, and mural nodules represent clonal evolution with selective divergence. DDMC is molecularly distinct, while novel mutations expand the spectrum of MTMN biology.
