Genomic Profile Of Clear Cell Ovarian Cancers And Evolution With Disease Progression

Introduction In clear cell ovarian cancers (CCOC) limited data is available on genomic evolution with disease progression. Methods 23 FFPE tumours collected from 12 patients with advanced CCOC, and 1 mixed clear cell endometrioid OC, treated at Auckland Hospital from 2003–2017, underwent whole exome sequencing (Macrogen), with matched normal tissue. Results 8 patients had diagnostic samples, 5 had diagnostic and first relapse samples, of these 2 had samples from a second relapse. 10/13 patients had 10 distinct ARID1A mutations, most were indels. In 3 patients ARID1A mutations were present at diagnosis and relapse, in 1 patient ARID1A mutation was present at first and second relapse but absent at diagnosis. Other driver mutations were identified in PIK3CA 2/13, AKT1 2/13, PTEN 1/13, NOTCH1 1/13, SMARCA4 1/13, PPP2R1A 1/13, TP53 1/13 and ARID5B 1/13. Putative driver mutations in ACVR1B and IGF2R were seen in relapse and not diagnostic samples. Three patients had euploid tumours, the remainder had a range of aneuploidy, predominantly in chromosomes 8, 9, 16 and 19. Ploidy remained stable with relapse, except in one chemotherapy-naive patient, who was euploid at diagnosis, and developed loss of heterozygosity (LOH) in several chromosomes at relapse. Tumour mutational burden (TMB) ranged from 10 mutations per MB, with no clear trend with disease progression. In one patient TMB was higher in the primary compared with 2 metachronous metastatic sites. Conclusion There was little change in genomic characteristics with disease progression. One chemotherapy naive patient developed LOH and increased TMB at relapse.