Mutation analysis of BRCA1 and BRCA2 from 793 Korean patients with sporadic breast cancer

Abstract

To investigate the role of BRCA1 and BRCA2 mutations in Korean patients with sporadic breast cancer, 793 breast cancer patients were analyzed by denaturing high performance liquid chromatography and direct sequencing. The 793 breast cancer patients enrolled in this study had no family history of affected first- or second-degree relatives with breast and/or ovarian cancer. Seventy-nine different sequence variations were identified, of which 34 were novel. Fifteen deleterious mutations were detected in 20 out of 793 patients (2.5%): 11 frameshift mutations and 4 nonsense mutations (seven in BRCA1 and eight in BRCA2), and no recurrent or founder mutations were observed in BRCA mutation screening. However, three mutations (K467X, 3972delTGAG, and R2494X in BRCA2) were identified in other studies of the Korean population. Of 793 patients, the clinicopathological information was obtained in 135 patients, who included 20 deleterious mutation-positive and 115 deleterious mutation-negative groups. The median age at diagnosis, histologic type, histologic grade and T stage did not show statistically significant difference between these two groups. BRCA-mutation-associated tumors showed lower estrogen receptor, progesterone receptor, and HER-2/neu but higher p53 expression. Although poor prognostic features were noted in BRCA-associated tumors, we did not find statistically significant differences. The present study will be helpful in the evaluation of the need for the genetic screening of germline BRCA mutations and reliable genetic counseling for sporadic breast cancer patients.

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

“…These variations have not been reported in the SNP database (http://www.ncbi.nlm.nih.gov/snp) and eight have been reported in the BIC database but are of unknown clinical importance. Among the 13 unclassified variations, 11 variations have been found in previous normal control studies 8,10 and/or in the present study, but there is not reliable functional assay at present. Four different protein prediction programs (PolyPhen, SIFT, PANTHER and SVM) were used to predict the functional consequences of the mutations and obtain diverse results.…”

“…Han et al 8 Sporadic cases DHPLC and sequencing 2.5% (20/793) Ahn et al 9 High and that we did not observe founder mutations, whole-gene sequencing of both BRCA1 and BRCA2 genes should be the method of choice used to identify mutations in high-risk Korean patients.…”

“…Most previous studies of BRCA1/BRCA2 genes in Korea used performed two-step approaches, in which mutations are first scanned in a rapid manner, and then subjected to sequencing analysis when sequence alterations are detected. [6][7][8][9][10] Table 3 shows the mutation detection rates in the BRCA1/BRCA2 genes from each study in Korea. Compared with the two studies using similar inclusion criteria for the high-risk group of Korean breast cancer patients, mutation detection rates of whole-gene sequencing exceeded 20%.…”

“…5 To date, only a few studies have examined the frequencies and spectra of mutations in large series of Korean breast cancer patients. [6][7][8][9][10] Several mutations are considered to be founder mutations, as they account for the majority of detected BRCA1/BRCA2 mutations in Korea. Although some of these recurrent mutations are unique to Koreans, their effects vary across studies.…”

Breast Cancer Associated Mutations Reported Among Malaysian Malay, Chinese and Indian Patients

“…A missense mutation T1723P, a synonymous mutation (L2647L) and a frameshift mutation (490 delCT) were found to be present only in MM case cohort [10][11][12] . A synonymous mutation (E425E) and a frameshift mutations (2001 del4) that were detected only in MC patients [10,11] were also reported in Korean breast cancer patients [34] . Han Chinese population was reported to carry only the 2001 del4 frameshift mutation and not both [35] .…”