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

• Yoo J
• Lee GD
• Kim JH
• Lee SN
• Chae H
• Han E
• Kim Y
• Kim M

• KMID: 2460912
• DOI: http://doi.org/10.3343/alm.2020.40.2.148

Abstract

BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
Multi-gene panel testing could be a significant screening tool for HBOC patients, especially for those with a family history of cancer.

Keyword

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
Humans
Mass Screening
Multiplex Polymerase Chain Reaction

Figure

• 

  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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