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Background <p>Mutations in the <i>BRCA1</i> and <i>BRCA2</i> genes play a pivotal role in the pathogenesis of breast, ovarian, prostate, pancreatic, and several other cancers. Identification of these mutations is crucial for selecting patients eligible for targeted therapy. In Vietnam, large-scale data on <i>BRCA1</i>/2 mutation prevalence and clinical utility are limited. We aim to report the prevalence of <i>BRCA1</i>/2 mutations across different cancer types, evaluate the effectiveness of next-generation sequencing (NGS) in copy-number variant detection, and discuss the clinical significance of the findings.</p> Methods <p>A total of 1,101 Vietnamese patients diagnosed with breast, ovarian, prostate, or pancreatic cancer underwent <i>BRCA1</i>/2 mutation test at Vinmec. The test utilized the AmoyDx BRCA-PRO KIT and the Illumina NextSeq 550 NGS platform. Copy-number variants were detected by NGS solely in blood-derived DNA samples and were systematically confirmed by MLPA.</p> Results <p>Among 1,101 unselected patients with breast, ovarian, prostate, or pancreatic cancer, pathogenic <i>BRCA1</i>/2 variants were identified in 158 (14.35%), including 57/158 of ovarian, 78/158 triple‑negative, 16/158 of prostate, 4/158 of pancreatic and 3/158 HR-positive breast cancer. The mutation burden was highest in ovarian cancer and TNBC, where <i>BRCA1</i> variants predominated over <i>BRCA2</i> (40/57 <i>BRCA1</i> vs 17/57 <i>BRCA2</i> in ovarian cancer and 57/78 <i>BRCA1</i> vs 21/78 <i>BRCA2</i> in TNBC). Several <i>BRCA1</i> truncating variants (c.4997dup, c.5251C &gt; T, c.5335del) and recurrent <i>BRCA2</i> loss‑of‑function variants were enriched in triple‑negative breast cancer (TNBC), with additional cases observed in ovarian, prostate, and pancreatic cancers. Notably, two heterozygous copy‑number losses were observed in our series: <i>BRCA1</i> exon 2 deletion (three TNBC and one ovarian cancer) and <i>BRCA2</i> exon 22–23 deletion (one TNBC and one prostate cancer).</p> Conclusions <p>This study provides one of the first large next-generation sequencing—based <i>BRCA1</i>/2 datasets in Vietnam, indicating a sizable subset of tumors with homologous recombination deficiency and potential sensitivity to PARP inhibitors and platinum‑based chemotherapy. These findings underscore the clinical utility of NGS‑based <i>BRCA1</i>/2 genotyping for therapeutic decision‑making and hereditary risk assessment across multiple tumor types and highlight the need for further research on long-term clinical outcomes.</p>

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Next-generation sequencing-based characterization of BRCA1/2 variants across multiple tumor types in Vietnamese patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月17日

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  • Hong-Thanh Nguyen,
  • Minh-Duc Vu,
  • Dinh-Dung Nguyen,
  • Phuong-Nhung Dinh,
  • Van-Quy Hoang,
  • Linh-Trang Ngoc Bui,
  • Dinh-Tuan Nguyen,
  • Phuoc-Huy Do,
  • Thi-Oanh Tong,
  • Van-Hung Nguyen,
  • Thu-Huong Thi Han,
  • Sy-Tung Ha,
  • Huy-Duong Do,
  • Thanh-Ha Thi Ly,
  • Viet-Nhan Nguyen

摘要

Background

Mutations in the BRCA1 and BRCA2 genes play a pivotal role in the pathogenesis of breast, ovarian, prostate, pancreatic, and several other cancers. Identification of these mutations is crucial for selecting patients eligible for targeted therapy. In Vietnam, large-scale data on BRCA1/2 mutation prevalence and clinical utility are limited. We aim to report the prevalence of BRCA1/2 mutations across different cancer types, evaluate the effectiveness of next-generation sequencing (NGS) in copy-number variant detection, and discuss the clinical significance of the findings.

Methods

A total of 1,101 Vietnamese patients diagnosed with breast, ovarian, prostate, or pancreatic cancer underwent BRCA1/2 mutation test at Vinmec. The test utilized the AmoyDx BRCA-PRO KIT and the Illumina NextSeq 550 NGS platform. Copy-number variants were detected by NGS solely in blood-derived DNA samples and were systematically confirmed by MLPA.

Results

Among 1,101 unselected patients with breast, ovarian, prostate, or pancreatic cancer, pathogenic BRCA1/2 variants were identified in 158 (14.35%), including 57/158 of ovarian, 78/158 triple‑negative, 16/158 of prostate, 4/158 of pancreatic and 3/158 HR-positive breast cancer. The mutation burden was highest in ovarian cancer and TNBC, where BRCA1 variants predominated over BRCA2 (40/57 BRCA1 vs 17/57 BRCA2 in ovarian cancer and 57/78 BRCA1 vs 21/78 BRCA2 in TNBC). Several BRCA1 truncating variants (c.4997dup, c.5251C > T, c.5335del) and recurrent BRCA2 loss‑of‑function variants were enriched in triple‑negative breast cancer (TNBC), with additional cases observed in ovarian, prostate, and pancreatic cancers. Notably, two heterozygous copy‑number losses were observed in our series: BRCA1 exon 2 deletion (three TNBC and one ovarian cancer) and BRCA2 exon 22–23 deletion (one TNBC and one prostate cancer).

Conclusions

This study provides one of the first large next-generation sequencing—based BRCA1/2 datasets in Vietnam, indicating a sizable subset of tumors with homologous recombination deficiency and potential sensitivity to PARP inhibitors and platinum‑based chemotherapy. These findings underscore the clinical utility of NGS‑based BRCA1/2 genotyping for therapeutic decision‑making and hereditary risk assessment across multiple tumor types and highlight the need for further research on long-term clinical outcomes.