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Abstract：
BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women. Although many studies have reported the BRCA mutations among breast cancer patients, few studies have focused among Chinese early-onset breast cancer patients. The purpose of this study is to identify BRCA1 and BRCA2 mutation features and their clinical significance of early-onset Chinese breast cancer patients.
METHODS: A total of 54 female patients diagnosed with breast cancer were enrolled in this study, of which 27 were younger than 40 (study group, mean age 32 years, range, 23-40 years) and 27 were older than 40 (control group, mean age 52 years, range, 41-68 years). Tumor FFPE samples were collected for somatic mutation test, while blood samples or normal tissue were used for germline mutation by both PGM and Miseq platform. All codon exons and functional introns for BRCA1/2 were covered. The clinical significance of mutation types was cross analyzed in several available database. The novel mutations were confirmed by sanger sequencing.
RESULTS: In study group, 14.8% (4/27) and 3.7% (1/27) patients had deleterious BRCA1/2 germline and somatic mutations respectively. While in control group, only 3.7% (1/27) and 7.4% (2/27) had deleterious BRCA1/2 germline and somatic mutations respectively. BRCA1 germline mutation c.2623C>T and BRCA2 germline mutation c.5852G>A were found to be novel mutation sites and confirmed by sanger sequencing.
CONCLUSIONS: Our study found two novel BRCA1/2 mutation sites in early-onset breast cancer, and also showed that early-onset breast cancer patients are more likely to harbor germline mutations with deleterious and uncertain significance.
METHODS: A total of 54 female patients diagnosed with breast cancer were enrolled in this study, of which 27 were younger than 40 (study group, mean age 32 years, range, 23-40 years) and 27 were older than 40 (control group, mean age 52 years, range, 41-68 years). Tumor FFPE samples were collected for somatic mutation test, while blood samples or normal tissue were used for germline mutation by both PGM and Miseq platform. All codon exons and functional introns for BRCA1/2 were covered. The clinical significance of mutation types was cross analyzed in several available database. The novel mutations were confirmed by sanger sequencing.
RESULTS: In study group, 14.8% (4/27) and 3.7% (1/27) patients had deleterious BRCA1/2 germline and somatic mutations respectively. While in control group, only 3.7% (1/27) and 7.4% (2/27) had deleterious BRCA1/2 germline and somatic mutations respectively. BRCA1 germline mutation c.2623C>T and BRCA2 germline mutation c.5852G>A were found to be novel mutation sites and confirmed by sanger sequencing.
CONCLUSIONS: Our study found two novel BRCA1/2 mutation sites in early-onset breast cancer, and also showed that early-onset breast cancer patients are more likely to harbor germline mutations with deleterious and uncertain significance.
摘要：
背景：乳腺癌是女性中最常见的癌症。尽管许多研究报道了乳腺癌患者的BRCA突变，很少有研究关注中国早发性乳腺癌患者。本研究的目的是确定早发性乳腺癌患者的BRCA1和BRCA2突变特征及其临床意义。
方法：本研究共纳入54例诊断为乳腺癌的女性患者，其中27人年龄小于40岁(研究组，平均年龄32岁,范围,23-40岁）和27岁以上40岁（对照组，平均年龄52岁,范围,41-68岁）。收集肿瘤FFPE样本进行体细胞突变测试，同时使用血液样本或正常组织通过PGM和Miseq平台进行种系突变。覆盖BRCA1/2的所有密码子外显子和功能性内含子。在几个可用的数据库中交叉分析了突变类型的临床意义。通过sanger测序证实了新的突变。
结果：在研究组中，14.8％（4/27）和3.7％（1/27）的患者分别存在有害的BRCA1/2种系和体细胞突变。而在对照组中，分别只有3.7%(1/27)和7.4%(2/27)的BRCA1/2种系和体细胞突变.发现BRCA1种系突变c.2623C>T和BRCA2种系突变c.5852G>A是新的突变位点，并通过sanger测序证实。
结论：我们的研究在早发性乳腺癌中发现了两个新的BRCA1/2突变位点，并且还表明早发性乳腺癌患者更有可能携带具有有害和不确定意义的种系突变。
方法：本研究共纳入54例诊断为乳腺癌的女性患者，其中27人年龄小于40岁(研究组，平均年龄32岁,范围,23-40岁）和27岁以上40岁（对照组，平均年龄52岁,范围,41-68岁）。收集肿瘤FFPE样本进行体细胞突变测试，同时使用血液样本或正常组织通过PGM和Miseq平台进行种系突变。覆盖BRCA1/2的所有密码子外显子和功能性内含子。在几个可用的数据库中交叉分析了突变类型的临床意义。通过sanger测序证实了新的突变。
结果：在研究组中，14.8％（4/27）和3.7％（1/27）的患者分别存在有害的BRCA1/2种系和体细胞突变。而在对照组中，分别只有3.7%(1/27)和7.4%(2/27)的BRCA1/2种系和体细胞突变.发现BRCA1种系突变c.2623C>T和BRCA2种系突变c.5852G>A是新的突变位点，并通过sanger测序证实。
结论：我们的研究在早发性乳腺癌中发现了两个新的BRCA1/2突变位点，并且还表明早发性乳腺癌患者更有可能携带具有有害和不确定意义的种系突变。
