Genomic landscapes of ovarian clear cell carcinoma from Latin countries reveal aberrations linked to survival and progression

Abstract

Abstract Background Ovarian clear cell carcinomas (OCCCs) are rare, aggressive and chemoresistant tumors. Geographical and ethnic differences in the incidence of OCCC have been reported with a higher incidence in Asiatic countries. There is a paucity of information regarding OCCC in Latin America (LA) and other countries. Methods Here, we characterized two cohorts of 33 patients with OCCC from LA (24 from Brazil and 9 from Costa Rica) and a cohort of 27 patients from Spain. Genomic analysis was performed for 26 OCCC using the OncoScan platform. Tumors were classified according to their genomic landscapes into the Simplex-like (Sxl), Firestorm-like (FSl) and Sawtooth-like (STl) subgroups. Results The median overall survival (OS) was not significantly different between the cohorts. Genomic landscapes were characterized by different homologous recombination deficiency (HRD) levels. OCCCs with MYC-amplified tumors bearing a concomitant loss of a region in chromosome 13q12-q13 that includes the BRCA2 gene (MB subgroup) had the longest OS. In contrast, non-MB patients carrying a high number (> 30) of total copy number (CN) aberrations presented the shortest OS (PS subgroup). Furthermore, amplification of the ASH1L gene was also associated with a shorter OS. No difference in the distribution of genomic landscapes or MB and PS profiles was detected between patients from the different cohorts. Initial-stage OCCCs with early progression were characterized by gains in the JNK1 and MKL1 genes. Conclusions Our results provide new data from understudied OCCC populations and reveal new potential markers and therapeutic targets for OCCCs.