Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues
Objective: The therapeutic effect of poly (ADP-ribose) polymerase (PARP) inhibitors in patients with epithelial ovarian cancer (EOC) with somatic BRCA mutations is consistent with that observed in patients with germline BRCA mutations, indicating the importance of detecting both germline and somatic...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Taiwanese Journal of Obstetrics & Gynecology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1028455922003448 |
| _version_ | 1797938724140482560 |
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| author | Eun Taeg Kim Ha Eun Jeong Hyung Joon Yoon Ki Hyung Kim Dong Soo Suh |
| author_facet | Eun Taeg Kim Ha Eun Jeong Hyung Joon Yoon Ki Hyung Kim Dong Soo Suh |
| author_sort | Eun Taeg Kim |
| collection | DOAJ |
| description | Objective: The therapeutic effect of poly (ADP-ribose) polymerase (PARP) inhibitors in patients with epithelial ovarian cancer (EOC) with somatic BRCA mutations is consistent with that observed in patients with germline BRCA mutations, indicating the importance of detecting both germline and somatic BRCA mutations concurrently. We compared the efficacy of multi-gene panel next generation sequencing (NGS) in EOC patients’ formalin-fixed, paraffin-embedded (FFPE) tissue to that of conventional Sanger sequencing in blood samples. Materials and methods: This study included 48 patients with EOC, and both blood Sanger sequencing and FFPE tissue NGS were conducted in all of them. Clinical and pathological data were reviewed, including age at diagnosis, histology, and stage. Blood Sanger sequencing was performed using peripheral blood leukocytes. The target regions of 90 cancer-related genes were identified using FFPE tissue. Results: The median age of patients was 56.1 years, with serous carcinoma (n = 40, 83.3%) and stage III (n = 37, 77.1%) being the most common histology and International Federation of Gynecology and Obstetrics (FIGO) stage, respectively. FFPE tissue NGS identified ten pathogenic variants, including all eight pathogenic variants identified by blood Sanger sequencing and two additional pathogenic variants. Furthermore, FFPE tissue NGS identified 19 variants of uncertain significance (VUS), including all ten VUS identified by blood Sanger sequencing and nine additional VUS. Conclusion: The FFPE tissue multi-gene panel NGS had 100% sensitivity for detecting BRCA germline mutations and could detect additional somatic mutations. Furthermore, performing FFPE tissue multi-gene panel NGS followed by blood Sanger sequencing sequentially may help differentiate germline from somatic BRCA mutations for genetic counseling. |
| first_indexed | 2024-04-10T19:05:16Z |
| format | Article |
| id | doaj.art-1c46072d4c154378abdbf32c7f1535fa |
| institution | Directory Open Access Journal |
| issn | 1028-4559 |
| language | English |
| last_indexed | 2024-04-10T19:05:16Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Taiwanese Journal of Obstetrics & Gynecology |
| spelling | doaj.art-1c46072d4c154378abdbf32c7f1535fa2023-01-31T04:08:20ZengElsevierTaiwanese Journal of Obstetrics & Gynecology1028-45592023-01-016216670Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissuesEun Taeg Kim0Ha Eun Jeong1Hyung Joon Yoon2Ki Hyung Kim3Dong Soo Suh4Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, South KoreaDepartment of Obstetrics and Gynecology, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, South KoreaDepartment of Obstetrics and Gynecology, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, South KoreaDepartment of Obstetrics and Gynecology, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, South KoreaCorresponding author. Department of Obstetrics and Gynecology, Pusan National University Hospital, 179 Gudeok-Ro, Seo-Gu, Busan 49241, South Korea. Fax: +82 51-248-2384.; Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, South KoreaObjective: The therapeutic effect of poly (ADP-ribose) polymerase (PARP) inhibitors in patients with epithelial ovarian cancer (EOC) with somatic BRCA mutations is consistent with that observed in patients with germline BRCA mutations, indicating the importance of detecting both germline and somatic BRCA mutations concurrently. We compared the efficacy of multi-gene panel next generation sequencing (NGS) in EOC patients’ formalin-fixed, paraffin-embedded (FFPE) tissue to that of conventional Sanger sequencing in blood samples. Materials and methods: This study included 48 patients with EOC, and both blood Sanger sequencing and FFPE tissue NGS were conducted in all of them. Clinical and pathological data were reviewed, including age at diagnosis, histology, and stage. Blood Sanger sequencing was performed using peripheral blood leukocytes. The target regions of 90 cancer-related genes were identified using FFPE tissue. Results: The median age of patients was 56.1 years, with serous carcinoma (n = 40, 83.3%) and stage III (n = 37, 77.1%) being the most common histology and International Federation of Gynecology and Obstetrics (FIGO) stage, respectively. FFPE tissue NGS identified ten pathogenic variants, including all eight pathogenic variants identified by blood Sanger sequencing and two additional pathogenic variants. Furthermore, FFPE tissue NGS identified 19 variants of uncertain significance (VUS), including all ten VUS identified by blood Sanger sequencing and nine additional VUS. Conclusion: The FFPE tissue multi-gene panel NGS had 100% sensitivity for detecting BRCA germline mutations and could detect additional somatic mutations. Furthermore, performing FFPE tissue multi-gene panel NGS followed by blood Sanger sequencing sequentially may help differentiate germline from somatic BRCA mutations for genetic counseling.http://www.sciencedirect.com/science/article/pii/S1028455922003448BRCAEpithelial ovarian cancerGenetic counselingNext generation sequencingPoly(ADP-Ribose) polymerase inhibitorsSanger sequencing |
| spellingShingle | Eun Taeg Kim Ha Eun Jeong Hyung Joon Yoon Ki Hyung Kim Dong Soo Suh Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues Taiwanese Journal of Obstetrics & Gynecology BRCA Epithelial ovarian cancer Genetic counseling Next generation sequencing Poly(ADP-Ribose) polymerase inhibitors Sanger sequencing |
| title | Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues |
| title_full | Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues |
| title_fullStr | Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues |
| title_full_unstemmed | Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues |
| title_short | Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues |
| title_sort | validation of multi gene panel next generation sequencing for the detection of brca mutation in formalin fixed paraffin embedded epithelial ovarian cancer tissues |
| topic | BRCA Epithelial ovarian cancer Genetic counseling Next generation sequencing Poly(ADP-Ribose) polymerase inhibitors Sanger sequencing |
| url | http://www.sciencedirect.com/science/article/pii/S1028455922003448 |
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