Keimyung Med J.  2024 Jun;43(1):44-49. 10.46308/kmj.2023.00283.

Utility of Next-Generation Sequencing Panel Including Hereditary Breast and Ovarian Cancer-Related Genes for Pathogenic Variant Detection

• Lee JH
• Kim DH

• KMID: 2556370
• DOI: http://doi.org/10.46308/kmj.2023.00283

Abstract

Hereditary breast and ovarian cancer syndrome (HBOC) is an inherited disorder associated with a higher than normal risk of breast and ovarian cancer. Most HBOC patients possess certain pathogenic variants (PVs) in BRCA1/2 genes. However, studies have indicated that HBOC patients may also have PVs in other cancer-related genes. Therefore, we analyzed variants in BRCA1/2 and other hereditary cancer-related genes in suspected HBOC patients using the multi-gene next-generation sequencing (NGS) panel method. We enrolled a total of 148 patients with cancers related to HBOC including breast, ovarian, primary peritoneal, prostate, and fallopian tube cancer. The 48 multi-gene NGS assay was applied to all samples, and multiplex ligation-dependent probe amplification (MLPA) and direct sequencing were used to confirm variants in BRCA1/2 and Lynch syndrome-related genes. We identified 17 PVs or likely PVs in 148 participants (11.5%), with PVs in BRCA1/2 detected in 7 patients (4.7%). We found PVs other than BRCA1/2 in 10 patients through the NGS panel and MLPA (7.1%). Apart from BRCA1/2, the genes in which PVs were detected included RAD51D, MLH1, MSH2, and MSH6. The NGS method shows significant potential in diagnosing and treating suspected HBOC patients, particularly those who test negative for BRCA1/2 genes.

Keyword

Genes, BRCA1; Genes, BRCA2; Hereditary breast and ovarian cancer syndrome; High-throughput nucleotide sequencing