Multi-gene panel next generation sequencing is effective for detection of both germline and somatic BRCA mutation in epithelial ovarian cancer = Multi-gene panel next generation sequencing is effective for detection of both germline and somatic BRCA mutation in epithelial ovarian cancer

다국어 초록 (Multilingual Abstract)

Objective: We investigated the efficacy of multi-gene panel next generation sequencing (NGS) in formalin-fixed, paraffin-embedded (FFPE) tissue of epithelial ovarian cancer (EOC) patients compared to blood Sanger sequencing.
Methods: A total of 48 EOC patients were participated in this study. All of them were conducted both blood Sanger sequencing and tissue NGS, and 17 patients were BRCA mutants. Clinical and pathological data were retrospectively reviewed including age at diagnosis, histology and stage. Sanger sequencing was done using peripheral blood leukocytes and DNA extracted by Promega DNA purification kit. FFPE tissue was used to capture the target regions of 90 cancer-related genes by Illumina MiSeqDx instrument. The clinical significance of detected mutation was evaluated by aggregating several tools such as BIC and ClinVar database.
Results: The median age was 56.1 years old, and the most common histology and FIGO stage were serous carcinoma (n=40, 83.3%) and stage III (n=37, 77.1%), respectively. The majority (79.1%) of the 48 patients were non-carrier, but 8 patients (16.7%) had germline mutation and 2 patients (4.2%) had somatic mutation. Blood Sanger sequencing detected 8 pathogenic variants and 10 VUS, which mean germline mutation. Two pathogenic variants and 9 VUS detected in FFPE tissue NGS but not detected in blood Sanger sequencing are somatic mutation. A total of 18 variants were detected in blood Sanger sequencing, including 8 pathogenic variants and 10 variants of uncertain significance (VUS). In contrast, 29 variants were detected in FFPE tissue NGS, including 10 pathogenic variants and 19 VUS. FFPE tissue NGS detected all the mutation detected in blood Sanger sequencing. Moreover, tissue NGS detected 11 additional somatic mutation, including 2 pathogenic variants and 9 VUS.
Conclusion: FFPE tissue NGS is effective for detection of both germline and somatic mutation, therefore it has advantages in that it can detect additional somatic mutation compared to blood Sanger sequencing.