Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort

Tran, Van Thuan; Nguyen, Su; Pham, Xuan Dung; Phan, Thanh Hai; Nguyen, Van Chu; Nguyen, Hung; Doan, Phuong Thao Thi; Lê, Tuấn Anh; Nguyen, Bao Toan; Jasmine, Thanh Xuan; Nguyen, Duy; Nguyen, Hong-Dang Luu; Nguyễn, Như Gia; Xuan, Duy Nguyen; Tran, Vu Uyen; Nguyen, Hue Hanh Thi; Le, Minh-Tri; Nguyen, Yen Nhi; Do, Thanh Thuy Thi; Truong, Dinh Kiet; Tang, Hung Sang; Phan, Minh-Duy; Nguyen, Hoai-Nghia; Giang, Hoa; Tu, Lan N.

doi:10.3389/fonc.2021.789659

Cited by 5 publications

(5 citation statements)

References 35 publications

(43 reference statements)

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“…There were different hotspot mutations among other populations. They are as follows: BRCA1 c.5251C > T and c.4997dup in the Vietnamese population [ 19 ]; BRCA1 c.4508C > A, c.4065_4068delTCAA, and BRCA2 c.3109C > T, c.4829_4830delTG in the Pakistani population [ 20 ]; BRCA1 c.390C > A, c.3627dupA, and BRCA2 c.7480C > T, c.1399A > T in the Korean population [ 21 ]; BRCA1 c.5123C > A, c.211A > G, and BRCA2 c.2806_2809delAAAC, c.6024dupG in the Spanish population [ 22 ]; BRCA1 c.5123C > A, and BRCA2 c.6174delT in the Latin American and the Caribbean populations [ 23 ]; and BRCA1 c.211dupA, c.798_799delTT, and BRCA2 c.1310_1313delAAGA in the North African population [ 24 ]. In a recent meta-analysis of BRCA1 and BRCA2 gene variations in Chinese individuals, c.5470_5477delATTGGGCA, c.2612C > T, and c.3548A > G in BRCA1 , and c.3109C > T, c.2806_2809delAAAC, and c.5164_5165delAG in BRCA2 were the most common variants [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

“…There were different hotspot mutations among other populations. They are as follows: BRCA1 c.5251C > T and c.4997dup in the Vietnamese population [19]; BRCA1 c.4508C > A, c.4065_4068delTCAA, Hakka population, respectively. These results showed that the hotspots of pathogenic variants in the BRCA genes demonstrate showed race-specific and region-specific differences.…”

Section: Ethnicity Comparison Of Brca1 and Brca2 Pathogenic Variantsmentioning

confidence: 99%

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Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients

Zhang

et al. 2022

BMC Cancer

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Objective To investigate the prevalence and spectrum of BRCA1 and BRCA2 mutations in Chinese Hakka patients with breast and ovarian cancer. Methods A total of 1,664 breast or ovarian cancer patients were enrolled for genetic testing at our hospital. Germline mutations of the BRCA gene were analysed by next-generation sequencing, including the coding regions and exon intron boundary regions. Results The 1,664 patients included 1,415 (85.04%) breast cancer patients and 245 (14.72%) ovarian cancer patients, while four (0.24%) patients had both the breast and ovarian cancers. A total of 151 variants, including 71 BRCA1 variants and 80 BRCA2 variants, were detected in the 234 (14.06%) patients. The 151 variants included 58 pathogenic variants, 8 likely pathogenic variants, and 85 variants of unknown significance (VUS). A total of 56.25% (18/32) and 65.38% (17/26) of pathogenic variants (likely pathogenic variants are not included) were distributed in exon 14 of BRCA1 and exon 11 of BRCA2, respectively. The most common pathogenic variants among this Hakka population are c.2635G > T (p.Glu879*) (n = 7) in the BRCA1 gene and c.5164_5165del (p.Ser1722Tyrfs*4) (n = 7) in the BRCA2 gene among the Hakka population. A hotspot mutation in the Chinese population, the BRCA1 c.5470_5477del variant was not found in this Hakka population. The prevalence and spectrum of variants in the BRCA genes in the Hakka patients are different from that in other ethnic groups. Conclusions The most common pathogenic variant in this population is c.2635G > T in the BRCA1 gene, and c.5164_5165delAG in the BRCA2 gene in this population. The prevalence and spectrum of variants in the BRCA1 and BRCA2 genes in the Hakka patients from southern China are different from those in other ethnic groups.

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Section: Resultsmentioning

confidence: 99%

“…There were different hotspot mutations among other populations. They are as follows: BRCA1 c.5251C > T and c.4997dup in the Vietnamese population [19]; BRCA1 c.4508C > A, c.4065_4068delTCAA, Hakka population, respectively. These results showed that the hotspots of pathogenic variants in the BRCA genes demonstrate showed race-specific and region-specific differences.…”

Section: Ethnicity Comparison Of Brca1 and Brca2 Pathogenic Variantsmentioning

confidence: 99%

Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients

Zhang

et al. 2022

BMC Cancer

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“…Genomic DNA was already isolated from FFPE and WBC samples as previous described [ ( Dang et al, 2020;Nguyen Hoang et al, 2023;Nguyen et al, 2022;Tran et al, 2021)]. DNA fragmentation and library preparation for paired FFPE and WBC samples were performed using the NEBNext Ultra II FS DNA library prep kit (New England Biolabs, USA) following the manufacturer's instructions.…”

Section: Library Preparation and Sequencing For Ffpe And Wbcmentioning

confidence: 99%

“…Germline variants were called from bam files of WBC samples by the DRAGENTM Germline pipeline. Variants were then classified according to the guidelines of The American College of Medical Genetics and Genomics (ACMG) as previously described [ (Tran et al, 2021;]. Pathogenic and likely pathogenic variants were reported.…”

Section: Bioinformatics Analysismentioning

confidence: 99%

Analytical validation and clinical utilization of K-4CARE™: a comprehensive genomic profiling assay with personalized MRD detection

Nguyen Hoang,

Nguyen,

Tran

et al. 2024

Front. Mol. Biosci.

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Background: Biomarker testing has gradually become standard of care in precision oncology to help physicians select optimal treatment for patients. Compared to single-gene or small gene panel testing, comprehensive genomic profiling (CGP) has emerged as a more time- and tissue-efficient method. This study demonstrated in-depth analytical validation of K-4CARE, a CGP assay that integrates circulating tumor DNA (ctDNA) tracking for residual cancer surveillance.Methods: The assay utilized a panel of 473 cancer-relevant genes with a total length of 1.7 Mb. Reference standards were used to evaluate limit of detection (LOD), concordance, sensitivity, specificity and precision of the assay to detect single nucleotide variants (SNVs), small insertion/deletions (Indels), gene amplification and fusion, microsatellite instability (MSI) and tumor mutational burden (TMB). The assay was then benchmarked against orthogonal methods using 155 clinical samples from 10 cancer types. In selected cancers, top tumor-derived somatic mutations, as ranked by our proprietary algorithm, were used to detect ctDNA in the plasma.Results: For detection of somatic SNVs and Indels, gene fusion and amplification, the assay had sensitivity of >99%, 94% and >99% respectively, and specificity of >99%. Detection of germline variants also achieved sensitivity and specificity of >99%. For TMB measurement, the correlation coefficient between whole-exome sequencing and our targeted panel was 97%. MSI analysis when benchmarked against polymerase chain reaction method showed sensitivity of 94% and specificity of >99%. The concordance between our assay and the TruSight Oncology 500 assay for detection of somatic variants, TMB and MSI measurement was 100%, 89%, and 98% respectively. When CGP-informed mutations were used to personalize ctDNA tracking, the detection rate of ctDNA in liquid biopsy was 79%, and clinical utility in cancer surveillance was demonstrated in 2 case studies.Conclusion: K-4CARE™ assay provides comprehensive and reliable genomic information that fulfills all guideline-based biomarker testing for both targeted therapy and immunotherapy. Integration of ctDNA tracking helps clinicians to further monitor treatment response and ultimately provide well-rounded care to cancer patients.

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“…According to the National Comprehensive Cancer Network (NCCN) guidelines, the genetic test now incorporates 17 non-BRCA genes (ATM, BARD1, BRIP1, CDH1, CHEK2, EPCAM, MSH2, MLH1, MSH6, NF1, PMS2, PALB2, PTEN, RAD51C, RAD51D, STK11, and TP53) for a comprehensive analysis of the patients [11][12][13] . Globally, there is a tendency to include these genes in large cohorts to elucidate the pathogenicity of HBOC and address better recommendations for patients and their families 14,15 .…”

Section: Introductionmentioning

confidence: 99%

Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population

Aguilar,

Garza-Rodríguez,

Muñiz-Garza

et al. 2024

Preprint

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Background: Hereditary predisposition to breast and ovarian cancer syndrome (HBOC) is a pathological condition with increased cancer risk, including breast (BC), ovarian cancer (OC), and others. HBOC pathogenesis is caused mainly by germline pathogenic variants (GPV) in BRCA1 and BRCA2 genes. However, other relevant genes are related to this syndrome diagnosis, prognosis, and treatment, including TP53, PALB2, CHEK2, ATM, etc. This study aimed to identify the prevalence of non-BRCA genes in HBOC patients of Northeast Mexico. Methods: This multicentric study included 1285 patients with HBOC diagnosis from four oncologic centers in northeast Mexico from 2016 to 2023. Genomic and clinical data were analyzed based on multi-gene panel results and electronic records of the medical geneticist consultation. For the data analysis of qualitative and quantitative variants JASP statistical software (version 0.18.1) was used, taking p<0.05 as a significant results. Results: We found that 32.7% of the patients had at least one GPV in non-BRCA genes. The five most frequent non-BRCA genes were CHEK2, PALB2, MUTYH, CDKN2A, and ATM. Among the group of non-BRCA genes, six are involved in the homologous repair pathway (HR), and three are related to DNA damage repair (DDR) pathways. In the analysis of GPVs in molecular pathways, DDR GPVs had a higher risk of developing BC and having cancer between 41-50 years. Conclusion: Multi-gene testing implementation improves the detection of often overlooked genes related to HBOC pathogenesis and treatment. Non-BRCA GPVs in Northern Mexico correspond to one-third of the HBOC cases, including HR and DDR pathways genes that would be misdiagnosed if not tested. HR patient carriers are potential targets of iPARP therapies. The optimal approach to cancer treatment for non-BRCA mutation carriers warrants further investigation to develop newer therapies.

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Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort

Cited by 5 publications

References 35 publications

Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients

Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients

Analytical validation and clinical utilization of K-4CARE™: a comprehensive genomic profiling assay with personalized MRD detection

Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population

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