Introduction Spatial heterogeneity in malignant tumors (heterogenous distribution of genetically diverse tumor subpopulations across different sites) is associated with resistance to treatment. The current study aimed to identify the spatial heterogeneity of the actionable genomic alterations (AGAs) in ovarian clear cell carcinoma (OCCC).
Methods Advanced OCCCs with four or more metastatic lesions resected at primary debulking surgery were included. Genomic DNA extracted from the formalin-fixed paraffin-embedded blocks of multiple cancerous lesions was analyzed by targeted deep sequencing with the custom panel including 84 OCCC-related genes. The genomic profiles of multiple cancerous lesions were compared to identify the spatial heterogeneity of the AGAs in individual cases.
Results Fifty cancerous lesions obtained from eight OCCCs were analyzed, and seventy-six potentially pathogenic variants (sixteen types of AGAs in six genes) were identified in five of eight OCCCs. Fifteen of sixteen AGAs in six genes, including ARID1A, PIK3CA, CTNNB1, TP53, PIK3R1, and KRAS, were shared across the primary and all metastatic lesions. However, in one case, the AGA of PIK3CA was only detected in the omental dissemination in which KRAS mutations were shown in all cancerous lesions.
Conclusion/Implications One AGA in PIK3CA showed spatial heterogeneity in advanced OCCC, suggesting that therapeutic strategies considering the spatial heterogeneity of the AGAs may be required in OCCC.
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