MUTYH c.892-2A>G剪切位点突变在家族性乳腺癌中的意义

The significance of MUTYH c.892-2A>G splicing mutation in familial breast cancer

背景与目的:MUTYH基因变异与结直肠癌患癌风险升高有关,但其突变与乳腺癌发生的相关性尚不明确,该研究探讨MUTYH c.892-2A>G剪切位点突变在中国家族性乳腺癌中的意义。方法:采用二代测序(next generation sequencing,NGS)方法检测95个家族性乳腺癌患者及亲属MUTYH基因突变情况,并与BRCA1、BRCA2基因突变情况进行比较。结果:95个家系224名受试者中有4个家系共7名受试者检出MUTYHc.892-2A>G突变,突变率为3.1%,其中只有1例先证者检出MUTYH c.892-2A>G突变。95个家系中也只有1例先证者检出携带BRCA1突变;5个家系中共9名受试者检出携带BRCA2突变,突变率为4.0%。MUTYH c.892-2A>G突变人数分别与BRCA2、BRCA1突变人数相比较,不存在基因共突变现象。结论:MUTYH c.892-2A>G突变虽然在有乳腺癌家族史的高危正常人群中突变率较高,但很可能是低外显的乳腺癌发生相关的致病位点。

Background and purpose： It is suggested that MUTYH mutation is closed to high colorectal cancer risk, but it is not clear that the relationship between MUTYH mutation and susceptibility to familiar breast carcinoma. The study was to investigate the significance of MUTYH c.892-2A〉G splicing mutation in familial breast cancer. Methods： The mutations of MUTYH,BRCA1 and BRCA2 genes were tested by the next generation sequencing （NGS） method in total of 224 participants, from 95 families with breast cancer patients （containing breast cancer patients and their relatives）, and then comparisons were carried out between them. The mutations detected by NGS were verifed by Sanger sequencing. Results： Seven participants from 4 families had a MUTYH c.892-2A〉G splicing mutation, with a mutation rate of 3.1% （7/224）, of which only one proband carried with this mutation. In 224 participants, only one proband carried with BRCA1 mutation. While 9 participants from 5 families had BRCA2 mutations, and their mutation rate was 4% （9/224）. Further the BRCA2 mutation site detected in the proband of every family was not the same. There were no signifcant diferences between the number of MUTYH c.892-2A〉G mutation and BRCA2 mutation or betweenthe number of MUTYH c.892-2A〉G mutation and BRCA 1 mutation. And there was no case which existed MUTYH and BRCAs gene co-mutations. Conclusion： Although its high mutation rate happens in the high-risk healthy population with a history of breast cancer, MUTYH c.892-2A〉G is likely to be a low penetrance gene mutation of susceptibility to breast cancer.