摘要
目的研究中国乳腺癌高风险人群中TP53基因胚系突变的情况。方法应用目标区域捕获和大规模平行测序的方法，对81个来自肿瘤高风险家系、BRCA1／2突变阴性的乳腺癌先证者基因组DNA进行TP53基因的突变检测。挑选候选突变进行Sanger测序验证及共分离研究。结果在81例BRCA1／2突变阴性的乳腺癌先证者中，分别在3例乳腺癌先证者中发现3个位于TP53外显子区的突变。其中两个为已知突变，一个为新发现的突变。1例TP53突变携带者的家族史符合Li—Fraumeni综合征的标准，占所有符合Li—Fraumeni综合征标准家系的9．1％（1／11）。2例TP53突变携带者诊断乳腺癌时的年龄小于30岁，占所有非常年轻乳腺癌患者（≤30岁）的11．8％（2／17）。结论TP53在中国乳腺癌高风险人群中有较高的检出率，提示在这一高危人群中，尤其是家族史符合Li—Fraumeni综合征标准的患者或BRCA1／2基因突变阴性的非常年轻乳腺癌患者应该接受TP53突变的检测。
Objective To evaluate the role of germline mutations of TP53 gene among a Chinese population with high risk for breast cancer. Methods A total of 81 BRCA-negative breast cancer probands from cancer families were analyzed using targeted capture and next-generation sequencing. Candidate mutations were verified with Sanger sequencing. Co-segregation analyses were carried out to explore the likely pathogenicity of the mutation. Results Of the 81 BRCA-negative patients, 3 exonic mutations in the TP53 gene were identified in 3 breast cancer patients. Of these, 2 mutations were previously reported and 1 was novel. One family with TP53 mutation has met the criteria for Li-Fraumeni syndrome （LFS） and accounted for 9.1% of all families who fulfilled the diagnostic criteria for LFS. Two of the carriers were diagnosed with breast cancer under the age of 30, and have accounted for 11.8% （2/17） of all very young （430 years） breast cancer patients in our study. Conclusion The TP53 germline mutation is more common in Chinese population with a high risk for breast cancer than previously thought. TP53 gene mutation screening should be considered particularly for patients with a family history of LFS and very young age of onset.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2015年第6期761-765,共5页
Chinese Journal of Medical Genetics
基金
上海市科委科技支撑项目（14441901402）
