Abstract
OBJECTIVE: This study identified genetic variations in ovarian tumor specimens from Filipino epithelial ovarian cancer (EOC) patients using next-generation sequencing. METHODS: Genomic DNA was isolated from formalin-fixed paraffin-embedded ovarian specimens from 8 chemosensitive and 8 chemoresistant EOC patients. Targeted next-generation sequencing was done to identify mutations in hotspot regions of common oncogenes and tumor-suppressor genes. The mutations were cross-referenced with dbSNP and ClinVar databases to identify previously reported alterations, and potentially damaging variants were predicted using PolyPhen-2. RESULTS: Our study has identified 85 unique variants, 35 in chemosensitive EOC, 22 in chemoresistant EOC, and 28 in both. Chemosensitive EOC specimens had more exonic single nucleotide variants than chemoresistant EOC specimens. Of the 50 oncogenes and tumor suppressor genes, KDR gene had the most frequent variations in EOC patients. Two of the unique KDR variants identified were novel mutations. Thirty-nine unique protein-modifying genetic variants were identified in all specimens, the majority of which have been previously reported in dbSNP and ClinVar. CONCLUSION: This study was the first non-BRCA genetic analysis done on ovarian cancer in Filipino patients. Next-generation sequencing was able to identify previously reported alterations with known therapeutic implications which may benefit from targeted therapy instead of standard chemotherapy regimen.