Spectra of BRCA1 and BRCA2 mutations in Korean patients with breast cancer: the importance of whole-gene sequencing

Abstract

The frequencies and spectra of germline mutations in the BRCA1 and BRCA2 genes vary among populations. In the present study, the mutation spectra of the BRCA1/BRCA2 genes in Korean breast cancer patients were investigated using whole-gene sequencing method. A total of 134 unrelated Korean breast cancer patients who were identified as being at high risk of carrying BRCA1/BRCA2 mutations were included. PCR amplification and direct sequencing were performed covering all exons and flanking intronic sequences of the BRCA1/BRCA2 genes. A total of 26 mutations were detected in 31 of 134 patients (23.1%). The mutation detection rate in the present study is higher than those of previous studies using screening methods (2.5-11.3%) and similar to that of a recent study, which used whole-gene sequencing (21.2%). The BRCA2: c.7480C4T mutation, which has been suggested to be a founder mutation in Koreans, was detected in only one patient. Five mutations were recurrent but observed in no more than two patients. Given that the mutation detection rates using whole-gene sequencing were much higher than for screening methods and that there were no consistent observations of founder mutations, whole-gene sequencing of both BRCA1 and BRCA2 genes should be the method of choice to identify mutations in high-risk Korean patients.

BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic‐related mutations in BRCA1 associated with an increased risk of ovarian cancer

“…The fact that it was recurrently found in patients with HBOC or ovarian cancer but not in general population (not recorded in the dbSNP and the 1,000 Genome Project databases) strongly supported its pathogenicity. All previously reported cases affected by this mutation were Asian patients from China and South Korea . This mutation seemed to be substantially enriched in Chinese populations and was reported mostly from HBOC breast cancer patients.…”

“…All previously reported cases affected by this mutation were Asian patients from China 20 and South Korea. 36,37 This mutation seemed to be substantially enriched in Chinese populations and was reported mostly from HBOC breast cancer patients. Based on data from cohorts of >200 patients, the incidence was reported to be 0.1% (1/505), 0.3% (2/625) and 0.4% (1/219).…”

Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls

“…ClinVar and SCRP also list three submissions with a VUS interpretation. Interestingly, other reports of this variant are restricted to studies using Korean cohorts, all of which classify the variant as VUS [ 12 , 22 - 24 ]. In our study, this variant was found in 11 cases and was the second most common mutation after BRCA1 c.3627dupA (12 cases).…”

High frequency of the recurrent c.1310_1313delAAGA BRCA2 mutation in the North-East of Morocco and implication for hereditary breast–ovarian cancer prevention and control

“…This common geographical distribution of the BRCA2 frameshift to close maghrebian countries (Algeria, Morocco and Tunisia) could be explained by geographical proximity and migration flow history. Much further from North-African area, the c.1310_1313delAAGA mutation, was carried by one Korean subject among the 31 patients with BRCA mutations of the 134 unrelated Korean hereditary breast cancer patients tested [21]. The c.1310_1313delAAGA presumably occurred several times at unstable mutational hot spots parts of the gene in different ethnic groups.…”