Variance of HRD score from primary to recurrent in high-grade serous ovarian cancer.

Abstract

e17540 Background: Homologous recombination deficiency (HRD) is an important biomarker of poly (ADP-ribose) polymerase inhibitor (PARPi) in patients with high-grade serous ovarian cancer (HGSOC). The stability of HRD in the recurrent HGSOC and its primary pair from Jiangsu Institute of Cancer Hospital was investigated. Methods: A total of paired 18 samples from 9 HGSOC patients were analyzed. HRD score was evaluated by loss of heterozygosity(LOH) and genetic mutations were also detected from next-generation sequencing.The student t-test evaluated the difference of HRD score between matched tumors. The functional annotation and clustering of affected genes in the recurrent tumor cells were analyzed by the KEGG Orthology (KO) database. Results: The HRD score of recurrent HGSOC tumors was significantly higher than that of the paired primary ones (p = 0.004). A total of 30 new somatic sequence variants at 27 genes presented in the recurrent tumors, were not found in any matched primary tumors. Of which, 19 (63.3%) were copy number variants (CNVs), 3 (10%) variants were rearrangement, and 8 (26.7%) were somatic point mutation. In these17 genes with CNVs, 14 genes had gene amplification variants, among them 50% (7/14) genes associated with the positive regulation of cell proliferation and cellular response to DNA damage stimulus. Four somatic point mutations involved in tumor suppressor pathway. Conclusions: Our data shed first light on the statistically significant changes of HRD score in paired recurrent HGSOC. The HRD score changes over time may imply further instantaneity assay strategy.