RT Journal Article
SR Electronic
T1 366 Genomic profile of clear cell ovarian cancers and evolution with disease progression
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP A150
OP A150
DO 10.1136/ijgc-2020-IGCS.316
VO 30
IS Suppl 3
A1 S Mesnage
A1 T Robb
A1 C Blenkiron
A1 K Payne
A1 H Hameed
A1 P Shields
A1 P Houseman
A1 M Findlay
A1 K Chrystal
A1 R Stephens
A1 C Print
A1 M Wilson
YR 2020
UL http://ijgc.bmj.com/content/30/Suppl_3/A150.2.abstract
AB 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-naïve patient, who was euploid at diagnosis, and developed loss of heterozygosity (LOH) in several chromosomes at relapse. Tumour mutational burden (TMB) ranged from <1 to >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 naïve patient developed LOH and increased TMB at relapse.