e17589 Background: With the recent approval of the KRAS pathway–targeted combination of avutometinib and defactinib for low-grade serous ovarian carcinoma, understanding the prevalence, genomic characteristics, and immunogenomic features of KRAS-altered ovarian cancer has become increasingly important. However, comprehensive data describing KRAS mutation patterns in Chinese ovarian cancer patients remain limited. This study aimed to characterize KRAS alterations and their associated genomic and immune-related features in a real-world Chinese ovarian cancer cohort to inform future precision treatment strategies. Methods: Next-generation sequencing (NGS) data from 625 ovarian cancers were analyzed for KRAS alterations, with immunogenomic features compared between KRAS-altered and wildtype tumors and across histological subtypes. Results: KRAS alterations were identified in 8.6% (54/625) of patients, including SNVs in 6.1% (38/625) and CNVs in 2.6% (16/625). No germline KRAS variants were detected. Most SNVs occurred in exon 2, with hotspot mutations at codons 12 and 13, consistent with classical activating KRAS variants. Patients with KRAS alterations were significantly younger than KRAS-wildtype patients (P = 0.002). The most frequent co-altered genes in KRAS-altered tumors were TP53 (57.4%) and PIK3CA (27.8%), suggesting concurrent dysregulation of cell-cycle and PI3K signaling pathways. Histology-specific analysis revealed significant enrichment of KRAS alterations in clear cell carcinoma (20.0%, 4/20) and mucinous carcinoma/adenocarcinoma subtypes (6.1%, 2/33), highlighting potential subtype-specific therapeutic opportunities. Immunogenomic comparisons showed that HRD positivity was significantly lower in KRAS-altered tumors than in KRAS-wildtype tumors (24.1% vs 63.6%, P < 0.001), indicating limited overlap between KRAS-driven oncogenesis and homologous recombination deficiency. No MSI-high tumors were observed in the KRAS-altered group (0% vs 1.2%, P = 1.00). Median TMB was similar between KRAS-altered and wildtype tumors (5.03 vs 4.47 mut/Mb, P = 0.84), suggesting no apparent immunogenic advantage associated with KRAS alterations in ovarian cancer. Conclusions: KRAS alterations are less frequent in Chinese ovarian cancer and lack favorable immunogenomic features, suggesting limited benefit from immunotherapy combinations. However, their enrichment in clear cell carcinoma indicates a histology-specific opportunity for KRAS-targeted therapy. These findings provide a reference for the application in the treatment of ovarian cancer, and also highlight the necessity of further exploration of more genetic characteristics of ovarian cancer.
Yang et al. (Thu,) studied this question.