遗传性乳腺癌-卵巢癌综合征1例家系易感基因的初步筛选

Preliminary screening of susceptible genes in a family with hereditary breast cancer and ovarian cancer syndrome

目的对1例遗传性乳腺癌-卵巢癌综合征(hereditary breast and ovarian cancer syndrome,HBOC)家系的易感基因进行初步筛选。方法该家系4代46名成员中有4例为乳腺癌和卵巢癌双源肿瘤,1例为双侧卵巢癌。选择3个核心成员的血样进行全外显子组测序(whole exome sequencing,WES),对突变位点进行注释和分析。于TCGA(the cancer genome atlas)和GEO(gene expression omnibus)数据库下载乳腺癌和卵巢癌患者资料,分析mRNA表达数据。结果 WES筛选的突变位点进行db SNP过滤,得到可能跟疾病相关的16个突变基因。继而在其余7个家系成员中进行重测序验证,发病者中均有FAM83E基因突变(NM-017708:p.Ser387Gly)。通过生物信息学分析TCGA和GEO数据,发现FAM83E基因在乳腺癌和卵巢癌组织中的表达,较正常组织明显升高。结论 FAM83E基因可能在乳腺癌和卵巢癌发生发展中具有重要作用,值得进一步研究。

Objective To screen the susceptibility genes of a family with hereditary breast and ovarian cancer syndrome（ HBOC）.Methods Four of 46 members of the 4-generation pedigree suffered from dual-tumor of breast and ovarian cancer,and one was bilateral ovarian cancer. Whole exome sequencing（ WES） was performed in three core members,and their mutations were annotated and analyzed. The data of breast cancer and ovarian cancer patients were downloaded from the cancer genome atlas（ TCGA） and gene expression omnibus（ GEO） databases to analyze mRNA expression data. Results The mutation sites of WES were screened by db SNP,and16 mutated genes related to disease were obtained. The FAM83 E gene mutation（ NM-017708： p. Ser387 Gly） was validated in all the present patients by re-sequencing of the other seven members. Further bioinformatics analysis of TCGA and GEO data showed that FAM83 E gene expression in breast cancer and ovarian cancer was significantly higher than that in adjacent normal tissue. Conclusion FAM83 E gene may play an important role in the development of breast cancer and ovarian cancer,which is worthy of further study.