BRCA1 and BRCA2 mutations of 140 Chinese breast cancer patients with genetic high risk
Author(s): Yang Liuchun, Liu Xiaojing, Jin Yanwen, Jin Shujuan, Han Xiaowei, Pang Hanmin, Li Jianpeng, Meng Di, Zuo Si, Gong Yandong, Cao Cheng, Huang Yan, Jiang Jun
Pages: 69-73
Year: 2017 Issue: 2
Journal: Chinese Journal of Breast Disease(Electronic Version)
Keyword: Breast neoplasms; Genes; BRCA1; Genes; BRCA2; Mutation;
Abstract: Objective To investigate the BRCA1 and BRCA2 mutations in Chinese breast cancer patients with genetic high risk.Methods This was an exploratory study.According to the inclusion and exclusion standard, 140 breast cancer patients with genetic high risk in 307 Hospital of PLA from September 2014 to June 2016 were selected as objects.According to the immunohistochemical results, the patients were divided into triple negative breast cancer (TNBC) group (35 cases) and non-TNBC group (105 cases).The next-generation sequencing was used to test the sequences of 49 exons and adjacent parts in BRCA1 and BRCA2 of these patients.The detected pathogenic mutations were compared with the mutations recorded in Breast Cancer Information Core (BIC) and ClinVar databases to screen the newly discovered ones.x2 test was used to analyze the difference of pathogenic mutation rates between TNBC group and non-TNBC group.Results The mutation rate of BRCA1/2 was 21.4%(30/140), including 7.9% (11/140) in BRCA1 and 13.8% (19/140) in BRCA2.There were 20 new mutations (17_18delAA, 1535_1536insATGA, 2013_2014insGT, 3266delT, 3458delT in BRCA1, and 1527delA, 2059_2063delGATTA, 2440delC, 3919G>T, 5461dupA, 6304delG, 6368dupA, 6446_6447insTA, 6552delG, 8016dupA, 8800C>T, 8942_8943delAA, 8899delA, 9070_9073delAACA, 9274_9277delTATT in BRCA2), which had never been reported in BIC and ClinVar databases.BRCA1 c.5470_5477delTGCCCAAT was found in one patient.The frequency of BRCA1/2 mutation in TNBC patients was 34.3% (12/35), significantly higher than 17.1% (18/105) in non-TNBC patients (x2=4.582, P=0.032).BRCA1 mutation rate was 31.43% (11/35) in TNBC patients, 0 (0/105) in non-TNBC patients, indicating a significant difference between two groups (x2=31.604,P<0.001).BRCA2 mutation rate was 2.86% (1/35) in TNBC patients, 17.14% (18/105) in non-TNBC patients, indicating no significant difference between two groups (x2=3.430,P=0.064).Conclusions Twenty newly discovered mutations may be unique in Chinese population, which enriches the spectrum of BRCA1/2 mutations in Chinese people.BRCA1 c.5470 _5477delTGCCCAAT may be the founder mutation in Chinese, which needs to be further confirmed.The doctors should pay attention to BRCA1/2 mutations in breast cancer patients with genetic high risk, especially in TNBC patients.TNBC patients with genetic high risk have relatively high mutation rate of BRCA1.
Pages: 69-73
Year: 2017 Issue: 2
Journal: Chinese Journal of Breast Disease(Electronic Version)
Keyword: Breast neoplasms; Genes; BRCA1; Genes; BRCA2; Mutation;
Abstract: Objective To investigate the BRCA1 and BRCA2 mutations in Chinese breast cancer patients with genetic high risk.Methods This was an exploratory study.According to the inclusion and exclusion standard, 140 breast cancer patients with genetic high risk in 307 Hospital of PLA from September 2014 to June 2016 were selected as objects.According to the immunohistochemical results, the patients were divided into triple negative breast cancer (TNBC) group (35 cases) and non-TNBC group (105 cases).The next-generation sequencing was used to test the sequences of 49 exons and adjacent parts in BRCA1 and BRCA2 of these patients.The detected pathogenic mutations were compared with the mutations recorded in Breast Cancer Information Core (BIC) and ClinVar databases to screen the newly discovered ones.x2 test was used to analyze the difference of pathogenic mutation rates between TNBC group and non-TNBC group.Results The mutation rate of BRCA1/2 was 21.4%(30/140), including 7.9% (11/140) in BRCA1 and 13.8% (19/140) in BRCA2.There were 20 new mutations (17_18delAA, 1535_1536insATGA, 2013_2014insGT, 3266delT, 3458delT in BRCA1, and 1527delA, 2059_2063delGATTA, 2440delC, 3919G>T, 5461dupA, 6304delG, 6368dupA, 6446_6447insTA, 6552delG, 8016dupA, 8800C>T, 8942_8943delAA, 8899delA, 9070_9073delAACA, 9274_9277delTATT in BRCA2), which had never been reported in BIC and ClinVar databases.BRCA1 c.5470_5477delTGCCCAAT was found in one patient.The frequency of BRCA1/2 mutation in TNBC patients was 34.3% (12/35), significantly higher than 17.1% (18/105) in non-TNBC patients (x2=4.582, P=0.032).BRCA1 mutation rate was 31.43% (11/35) in TNBC patients, 0 (0/105) in non-TNBC patients, indicating a significant difference between two groups (x2=31.604,P<0.001).BRCA2 mutation rate was 2.86% (1/35) in TNBC patients, 17.14% (18/105) in non-TNBC patients, indicating no significant difference between two groups (x2=3.430,P=0.064).Conclusions Twenty newly discovered mutations may be unique in Chinese population, which enriches the spectrum of BRCA1/2 mutations in Chinese people.BRCA1 c.5470 _5477delTGCCCAAT may be the founder mutation in Chinese, which needs to be further confirmed.The doctors should pay attention to BRCA1/2 mutations in breast cancer patients with genetic high risk, especially in TNBC patients.TNBC patients with genetic high risk have relatively high mutation rate of BRCA1.
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