J Gynecol Oncol.  2018 Nov;29(6):e90. 10.3802/jgo.2018.29.e90.

BRCA1/2 mutations, including large genomic rearrangements, among unselected ovarian cancer patients in Korea

• Kim DH
• Cho CH
• Kwon SY
• Ryoo NH
• Jeon DS
• Lee W
• Ha JS

• KMID: 2431235
• DOI: http://doi.org/10.3802/jgo.2018.29.e90

Abstract

OBJECTIVE
We performed small-scale mutation and large genomic rearrangement (LGR) analysis of BRCA1/2 in ovarian cancer patients to determine the prevalence and the characteristics of the mutations.
METHODS
All ovarian cancer patients who visited a single institution between September 2015 and April 2017 were included. Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and long-range polymerase chain reaction (PCR) were performed to comprehensively study BRCA1/2. The genetic risk models BRCAPRO, Myriad, and BOADICEA were used to evaluate the mutation analysis.
RESULTS
In total, 131 patients were enrolled. Of the 131 patients, Sanger sequencing identified 16 different BRCA1/2 small-scale mutations in 20 patients (15.3%). Two novel nonsense mutations were detected in 2 patients with a serous borderline tumor and a large-cell neuroendocrine carcinoma. MLPA analysis of BRCA1/2 in Sanger-negative patients revealed 2 LGRs. The LGRs accounted for 14.3% of all identified BRCA1 mutations, and the prevalence of LGRs identified in this study was 1.8% in 111 Sanger-negative patients. The genetic risk models showed statistically significant differences between mutation carriers and non-carriers. The 2 patients with LGRs had at least one blood relative with breast or ovarian cancer.
CONCLUSION
Twenty-two (16.8%) of the unselected ovarian cancer patients had BRCA1/2 mutations that were detected through comprehensive BRCA1/2 genetic testing. Ovarian cancer patients with Sanger-negative results should be considered for LGR detection if they have one blood relative with breast or ovarian cancer. The detection of more BRCA1/2 mutations in patients is important for efforts to provide targeted therapy to ovarian cancer patients.

Keyword

Mutation; Genes; Neoplasms; Ovary; Korea

MeSH Terms

Breast
Carcinoma, Neuroendocrine
Codon, Nonsense
Female
Genetic Testing
Humans
Korea*
Multiplex Polymerase Chain Reaction
Ovarian Neoplasms*
Ovary
Polymerase Chain Reaction
Prevalence
Codon, Nonsense