Ovarian carcinomas (OCs) are highly sensitive to platinum-based therapy, however most of OCs eventually relapse. This study aimed to compare genomic profiles in primary vs. recurrent OCs.
Primary, recurrent and normal tissue triplets obtained from 15 patients were subjected to exome sequencing. The comparison included 1) spectrum of driver mutations [Tamborero et al., 2018; PMID: 29592813]; 2) tumor mutation burden (TMB); 3) HRD score [Telli et al., 2016; PMID: 26957554]; 4) mutational signatures [Degasperi et al., 2020; PMID: 32118208].
All driver mutation present in primary tumors remained in the genome through the treatment course. One or several new driver somatic mutations emerged in 6/15 (40%) recurrent lesions. These alterations involved RB1 and ELAC2 (n = 1), TNC (n = 1), TRIO and IKBKB (n = 1), PAX5 and CDH10 (n = 1), SOX9 (n = 1), ABCB4 and EEF1A1 (n = 1) genes. Recurrent tumors demonstrated small but statistically significant increase of TMB as compared to primary lesions (4.7 vs. 3.9 per megabase, p = 0.01). HRD demonstrated high degree of similarity within primary/recurrent tumor pairs. PLATINUM mutation signature was characteristic for platinum-sensitive relapses, but not for platinum-resistant recurrences or chemonaive tumors (p = 0.02).
HRD score remains stable through the treatment history. PLATINUM mutation signature reflects not only the mere fact of prior exposure to platinum-based therapy, but also the efficacy of this therapeutic regimen.
The authors.
Russian Science Foundation, grant 21-75-30015.
All authors have declared no conflicts of interest.