Article Text
Abstract
Introduction We explored the genomic profiles of advanced high-grade serous carcinoma (HGSC) in patients who underwent suboptimal cytoreduction and had long survival outcomes.
Methods Patients with advanced HGSC who underwent suboptimal primary cytoreduction and had OS >10 years were retrospectively identified. OS was defined from the date of initial surgery to date of death or last follow-up. Whole-genome sequencing was performed. Bioinformatic analyses included the assessment of somatic mutations, copy number alterations, rearrangements, mutational signatures, and homologous recombination deficiency (HRD).
Results Six patients were included, with a median age of 68 years (range, 56-73). Five patients had stage IIIC disease and 1 had stage IV disease. All patients were treated with platinum-taxane doublet chemotherapy. Median time to recurrence (n=5) was 33.3 months (range, 14.5-60.8). Three patients died of their disease (OS range, 128.4-141.4 months). Surviving patients have OS ranging from 133.3 to 141.2 months. Three patients had a TP53 biallelic somatic mutation. All patients but one had high levels of genomic instability, with a median fraction of genome altered of 66% (range, 54%-80%). All tumors but one displayed genomic features of HRD. In addition to 1 germline BRCA2 mutation, homozygous deletions affecting the HR-related genes BRCC3 (n=2) and ATM (n=1) were found. All patients but one displayed mutational signatures 3 and/or 8, which are characteristic of HRD.
Conclusion/Implications Genomic features of HRD, which are generally found in approximately one-half of all HGSCs, were present in all tumors but one from patients with suboptimal cytoreduction who were studied, coupled with loss-of-function alterations in HRD-related genes.