Prevalence of pathogenic variants in actionable genes in advanced ovarian cancer: a next-generation sequencing analysis of a nationwide registry study

• Published in: European journal of cancer (1990) Vol. 141; pp. 185 - 192
• Main Authors: Kang, Sokbom, Yu, Ye L., Cho, Soo Y., Park, Seog-Yun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2020; Elsevier Science Ltd
• Subjects: BRCA1 protein; BRCA2 protein; Breast cancer; Cancer; Confidence intervals; ErbB-2 protein; Female; Genes; Genomic analysis; High-Throughput Nucleotide Sequencing; Humans; Mutation; Next-generation sequencing; Ovarian cancer; Ovarian Neoplasms - genetics; p53 Protein; Population studies; Prevalence; PTEN protein; Real-world data; Registries; Registry study; Republic of Korea; Sequence analysis; Sequence Analysis, DNA; TOR protein; Tumors; Republic of Korea; Next-generation sequencing; Genomic analysis; Mutation; Real-world data; Registry study; Ovarian cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2020.09.036

We examined the actionable genomic alterations in ovarian cancer by analysing the nationwide registry of next-generation sequencing (NGS) data. From March 2017 to December 2018, 16,458 patients with cancer underwent NGS testing under the interim coverage programme for NGS provided by the National Health Insurance of Korea. Among these patients, 779 patients had advanced ovarian cancer. Fifty-eight mutations were reported as pathogenic variants, which included likely pathogenic variants, and 55 theoretically actionable genes were analysed. The prevalence of pathogenic mutations in the population was 81.5%, whereas 11.6% of the population had neither a pathogenic mutation nor a variant of unknown significance. Common pathogenic mutations shared by at least 3% of the study population were mutations in TP53 (61.5%), BRCA1 (12.2%), PIK3CA (10.4%), KRAS (10.3%), BRCA2 (9.6%) and PTEN (3.7%). BRCA1/2 pathogenic mutations were found in 14.0% (42 of 300, 95% confidence interval = 10–18%) of the patients with TP53 wild-type tumours, comprising approximately one-quarter (25.9%) of the total observed BRCA1/2 pathogen mutations. At least one pathogenic mutation in a theoretically actionable gene was found in 49.2% of patients. Among patients without a BRCA1/2 pathogenic mutation, mutations were frequently observed in KRAS (12.2%), PIK3CA (10.4%) and PTEN (4.2%). PTCH1 mutations were correlated with ATM, NF1, ERBB2 and MTOR mutations (adjusted p = 0.0054, p = 0.0035, p = 0.0010 and p = 0.0003, respectively). Almost half of patients with ovarian cancer could be estimated as theoretical candidates for genomic medicine. Substantial BRCA1/2 pathogenic mutations were observed in patients not harbouring a TP53 mutation. •A nationwide next-generation sequencing registry of 779 patients with ovarian cancer was analysed.•At least one pathogenic mutation of the actionable genes was found in 49.2% of patients.•The comutations of TP53 and KRAS or PIK3CA were observed in 5% and 4% of patients, respectively.•Substantial BRCA1/2 mutations (25.9%) were found in patients without a TP53 mutation.•PTCH1 mutations were correlated with ATM, NF1, ERBB2 and MTOR mutations.