Germline mutational analysis of the C19orf62 gene in African-American women with breast cancer.
Germline mutational analysis of the C19orf62 gene in African-American women with breast cancer.
复制标题
DOI：
10.1007/s10549-011-1445-y
复制
发表时间：
2011-06
影响因子：
3.8
通讯作者：
Huo D
中科院分区：
文献类型：
--
作者：
Zheng Y;Zhang J;Niu Q;Olopade OI;Huo D
在过去的二十年中，乳腺癌遗传学领域取得了稳步进展，因为我们对肿瘤发生是如何从受损的DNA中产生的理解不断增加。在BRCA1和BRCA2作为乳腺癌风险指标占据中心位置的同时，我们继续确定其他易感基因和基因组区域，不断增加我们对乳腺癌病因学的理解。通过全基因组关联研究（GWAS），发现19p13位点与乳腺癌和卵巢癌风险有关。据报道，该区域含有一种名为C19orf62的基因，其蛋白质在DNA损伤修复中起着关键作用。在本研究中，对C19orf62基因进行了全测序，以筛选有害突变。在我们的110名家族性和144名非家族性非裔美国女性乳腺癌患者队列中，我们确定了35个DNA序列变异，包括4个错义变异，这些变异似乎不太可能引起疾病。我们在这个队列中没有检测到有害的移码截断或无义突变。我们的研究结果表明，在家族性和非家族性乳腺癌女性中，C19orf62的种系有害突变应该是罕见或不存在的。然而，C19orf62基因突变与乳腺癌风险相关的可能性值得在大量不同人群中进一步研究。
The past two decades have seen steady progress in the field of breast cancer genetics as we continually increase our understanding of how tumorigenesis results from damaged DNA. While BRCA1 and BRCA2 have taken center stage as indicators for breast cancer risk, we continue to identify other susceptibility genes and genomic regions, ever increasing our comprehension of breast cancer etiology. Through genome-wide association studies (GWAS), the 19p13 locus was found to contribute to breast and ovarian cancer risk. This region harbors a gene called C19orf62 whose protein has been reported to be a pivotal component in DNA damage repair. In the present study, complete sequencing was performed to screen for deleterious mutations in the C19orf62 gene. In our cohort of 110 familial and 144 non-familial African-American breast cancer female patients, we identified thirty-five DNA sequence variants, including four missense variants, which appeared unlikely to be disease-causing. We did not detect deleterious frameshift truncating or nonsense mutations in this cohort. Our findings suggest that germline deleterious mutations in C19orf62 should be rare or absent in familial and non-familial breast cancer women. However, the possibility that mutations in C19orf62 contribute to breast cancer risk warrant further studies in large diverse populations.