Recurrent BRCA1 Mutation, but no BRCA2 Mutation, in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing

Vũ, Hoàng Anh; Phú, Ngộ Đại; Khương, Lê Thái; Hòa, Phạm Huy; Nhu, Bùi Thị Hồng; Nhan, V.; Thanh, Lê Quang; Sinh, Nguyen Duy; Thanh, Hoàng; Quân, Nguyễn Đăng; Bình, Nguyễn Trọng

doi:10.31557/apjcp.2020.21.8.2331

Cited by 4 publications

(4 citation statements)

References 18 publications

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“…who used NGS to characterize all BRCA mutations in 101 Vietnamese patients with ovarian cancer. Their data showed that 6.9% (7/101) patients carried pathogenic mutations in BRCA1 and similar to our study, no BRCA2 mutation was identified ( 25 ). Another study in Vietnam involving 259 breast cancer patients reported only 2 carriers of BRCA mutations (0.8%) ( 26 ).…”

Section: Discussionsupporting

confidence: 91%

“…The most prevalent BRCA1 mutation was NM_007294.3:c.5251C>T (p.Arg1751Ter) as identified in 3 unrelated individuals. This mutation was previously proposed to be a founder mutation in the Vietnamese when it was identified in 4% (4/101) patients with ovarian cancer in Vietnam ( 25 ). However, it has also been reported as a founder or recurrent mutation in the Greek ( 31 ) and Polish ( 32 ), making it a recurrent rather than founder mutation in the Vietnamese.…”

Section: Discussionmentioning

confidence: 98%

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Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort

et al. 2022

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BackgroundHereditary cancer syndromes (HCS) are responsible for 5-10% of cancer cases. Genetic testing to identify pathogenic variants associated with cancer predisposition has not been routinely available in Vietnam. Consequently, the prevalence and genetic landscape of HCS remain unknown.Methods1165 Vietnamese individuals enrolled in genetic testing at our laboratory in 2020. We performed analysis of germline mutations in 17 high- and moderate- penetrance genes associated with HCS by next generation sequencing.ResultsA total of 41 pathogenic variants in 11 genes were detected in 3.2% individuals. The carrier frequency was 4.2% in people with family or personal history of cancer and 2.6% in those without history. The percentage of mutation carriers for hereditary colorectal cancer syndromes was 1.3% and for hereditary breast and ovarian cancer syndrome was 1.6%. BRCA1 and BRCA2 mutations were the most prevalent with the positive rate of 1.3% in the general cohort and 5.1% in breast or ovarian cancer patients. Most of BRCA1 mutations located at the BRCA C-terminus domains and the top recurrent mutation was NM_007294.3:c.5251C>T (p.Arg1751Ter). One novel variant NM_000038.6(APC):c.6665C>A (p.Pro2222His) was found in a breast cancer patient with a strong family history of cancer. A case study of hereditary cancer syndrome was illustrated to highlight the importance of genetic testing.ConclusionThis is the first largest analysis of carrier frequency and mutation spectrum of HCS in Vietnam. The findings demonstrate the clinical significance of multigene panel testing to identify carriers and their at-risk relatives for better cancer surveillance and management strategies.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 98%

Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort

et al. 2022

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“…In a recent Vietnam report of Hoang Anh Vu (2020), there were four types of pathogenic BRCA1 mutations in Vietnamese patients with ovarian cancer. Among these patients, BRCA1 : c.1621C > T was present in two patients, BRCA1 : c.5251C > T in four patients and BRCA1 : c.5335delC in one case [ 4 ]. In a study of 200 cases of Asian origin on breast cancer patients living in the USA, three in four Vietnamese patients were identified with the mutation c.5251C > T in BRCA1 [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…Patients benefit from platinum based chemotherapy and targeted treatment with Poly (ADP-ribose) polymerase (PARP) inhibitors [ 2 ], while unaffected family members may benefit from genetic counseling for HBOC, thereby obtaining timely screening and reducing surgery such as prophylactic mastectomy or salpingo-oophorectomy [ 3 ]. Although two studies of BRCA1/2 gene mutations in the Vietnamese population were reported solely on patients themselves or in breast cancer [ 4 , 5 ], there have been no evidence on the mutations of these genes in HBOC patients. To date, there has been no official practice guideline for the diagnosis of HBOC syndrome in Vietnam; however, available national guidelines for the treatment of breast and ovarian cancer recommend target therapy for these patients with BRCA1/2 gene mutations.…”

Section: Introductionmentioning

confidence: 99%

BRCA1/2 Mutations in Vietnamese Patients with Hereditary Breast and Ovarian Cancer Syndrome

Tran

Nguyen

et al. 2022

Genes

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(1) Background: Individuals with BRCA1/2 gene mutations are at increased risk of breast and ovarian cancer. The prevalence of BRCA1/2 mutations varies by race and ethnicity, and the prevalence and the risks associated with most BRCA1/2 mutations has not been unknown in the Vietnamese population. We herein screen the entire BRCA1 and BRCA2 genes for breast and ovarian cancer patients with a family history of breast cancer and ovarian cancer, thereby, suggesting a risk score associated with carrier status and history for aiding personalized treatment; (2) Methods: Between December 2017 and December 2019, Vietnamese patients who had a pathological diagnosis of breast and epithelial ovarian cancer were followed up, prospectively, after treatment from two large institutions in Vietnam. Blood samples from 33 Vietnamese patients with hereditary breast and ovarian cancers (HBOC) syndrome were collected and analyzed using Next Generation Sequencing; (3) Results: Eleven types of mutations in both BRCA1 (in nine patients) and BRCA2 (in three patients) were detected, two of which (BRCA1:p.Tyr1666Ter and BRCA2:p.Ser1341Ter) have not been previously documented in the literature. Seven out of 19 patient’s relatives had BRCA1/2 gene mutations. All selected patients were counselled about the likelihood of cancer rising and prophylactic screening and procedures. The study established a risk score associated with the cohorts based on carrier status and family history; (4) Conclusions: Our findings suggested the implications for the planning of a screening programme for BRCA1 and BRCA2 genes testing in breast and ovarian cancer patients and genetic screening in their relatives. BRCA1/2 mutation carriers without cancer should have early and regular cancer screening, and prophylactic measures. This study could be beneficial for a diverse group in a large population-specific cohort, related to HBOC Syndrome.

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Combination ofBRCAdeep targeted sequencing and shallow whole genome sequencing to detect homologous recombination deficiency in ovarian cancer

Nguyen,

Tran,

Nguyen

et al. 2024

Preprint

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BackgroundsAssessing homologous recombination deficiency (HRD) has been recommended by clinical guidelines for patients with ovarian cancer (OC) as it predicts sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). However, HRD testing is complex and either inaccessible or unaffordable for majority of OC patients in developing countries. Consequently, the prevalence of HRD in OC remains unknown.MethodsWe examined HRD status of 77 Vietnamese patients with OC using a new laboratory-developed test (HRD Insight, Gene Solutions). Tumor DNA was extracted from FFPE samples, followed by next-generation sequencing to detect deleterious or suspected deleterious variants inBRCA1/2genes. Shallow whole genome sequencing was performed to determine the whole Genomic Instability (wGI) score by assessing the presence of large-scale intra-chromosomal copy number alterations.ResultsThe assay was first benchmarked against commercial HRD kits including TruSight Oncology 500 HRD (Illumina), SOPHiA DDM HRD Solutions (Sophia Genetics) and HRD Focus Panel (AmoyDx), and showed an overall percent agreement of 90.0%, 96.3%, and 96.4% respectively. The successful rate of sequencing was 94.8% (73/77) and the prevalence of HRD in OC patients was 54.8% (40/73).BRCAmutations and positive wGI scores were found in 16.4% (12/73) and 47.9% (35/73) of the patients respectively. Among those with wild-typeBRCA1/2, 40.5% of them had positive wGI scores and hence positive HRD. Age at diagnosis was not affected by bothBRCAand wGI status.ConclusionsHRD Insight assay could accurately and robustly determine the HRD status of ovarian tissue samples, including those with low quality.

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Recurrent BRCA1 Mutation, but no BRCA2 Mutation, in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing

Cited by 4 publications

References 18 publications

Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort

Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort

BRCA1/2 Mutations in Vietnamese Patients with Hereditary Breast and Ovarian Cancer Syndrome

Combination ofBRCAdeep targeted sequencing and shallow whole genome sequencing to detect homologous recombination deficiency in ovarian cancer

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