Ann Lab Med.  2020 Mar;40(2):148-154. 10.3343/alm.2020.40.2.148.

Clinical Validity of Next-Generation Sequencing Multi-Gene Panel Testing for Detecting Pathogenic Variants in Patients With Hereditary Breast-Ovarian Cancer Syndrome

  • 1Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 2Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.


Hereditary breast and ovarian cancer syndrome (HBOC) is caused by pathogenic variants in BRCA and other cancer-related genes. We analyzed variants in BRCA gene and other cancer-related genes in HBOC patients to evaluate the clinical validity of next-generation sequencing (NGS) multi-gene panel testing.
The BRCA1/2 NGS testing was conducted for 262 HBOC patients. Multiplex ligation-dependent probe amplification and direct Sanger sequencing were performed for confirmation. Multi-gene panel testing was conducted for 120 patients who did not possess BRCA1/2 pathogenic variants but met the National Comprehensive Cancer Network criteria.
Pathogenic variants in BRCA1/2 were detected in 30 HBOC patients (11.5%). Additionally, four out of the 120 patients possessed pathogenic variants by multi-gene panel testing (3.3%): MSH2 (c.256G>T, p.Glu86*), PMS2 (c.1687C>T, p.Arg563*), CHEK2 (c.546C>A, p.Tyr182*), and PALB2 (c.3351-1G>C). All the four patients had a family history of cancer.
Multi-gene panel testing could be a significant screening tool for HBOC patients, especially for those with a family history of cancer.


Hereditary breast and ovarian cancer syndrome; BRCA1/2; Pathogenic variants; Multi-gene panel; Clinical validity; Next-generation sequencing

MeSH Terms

Hereditary Breast and Ovarian Cancer Syndrome
Mass Screening
Multiplex Polymerase Chain Reaction


  • Fig. 1 Scheme of BRCA1/2 and multi-gene NGS testing.Abbreviations: BRCA, BReast CAncer gene; NGS, next-generation sequencing; HBOC, hereditary breast and ovarian cancer; Pts, patients; MLPA, multiplex ligation-dependent probe amplification; NCCN, National Comprehensive Cancer Network.

  • Fig. 2 Pedigrees and confirmation in IGV and Sanger sequencing of pathogenic variants in multi-gene panel testing. (A) Pathogenic variant in CHEK2 and MSH2. (B) Pathogenic variants in PALB2 and PMS2.Abbreviation: IGV, Integrative Genomics Viewer.

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