技术专题

抗击乳腺癌的战斗是没有止境的，近日，弗吉尼亚理工大学的研究人员发现一种新的诊断标志物，可能有助于临床医生更好地预测和预防这种疾病。

八分之一的妇女在有生之年可能患乳腺癌，因此找到更好的预测指标非常重要。通过将乳腺癌血液样品基因组与无癌症个人的样本进行比较，研究人员精确定位了一些新的标记，不仅可以揭示乳腺癌风险，同时可能为乳腺癌的治疗产生益处。这项研究结果发表在Breast Cancer Research and Treatment杂志上。

研究人员发现两组样本之间微卫星的微小变化，微卫星是基因组中重复DNA的小区域，可以以各种不同的方式影响细胞功能。通常在过去，微卫星被称为“垃圾DNA”，但目前认为微卫星在许多疾病和基因突变中是重要的。一般情况下，在细胞复制过程中，发生的基因突变被DNA修复机制清理，但不是所有的都是，一些突变可能导致癌症。

新一代测序技术和新的分析工具让科学家能更深入地探讨DNA的暗物质，这可能会产生比目前使用的更可靠的新的标记物，以及可能的基因疗法。利用微卫星变异诊断有可能改变癌症和其他遗传性疾病的诊断和治疗方式。

PMC:
PMID:

Microsatellite genotyping reveals a signature in breast cancer exomes

L. J. McIver, N. C. Fonville, E. Karunasena, and H. R. Garner.

Genomic instability at microsatellite loci is a hallmark of many cancers, including breast cancer. However, much of the genomic variation and many of the hereditary components responsible for breast cancer remain undetected. We hypothesized that variation at microsatellites could provide additional genomic markers for breast cancer risk assessment. A total of 1,345 germline and tumor DNA samples from individuals diagnosed with breast cancer, exome sequenced as part of The Cancer Genome Atlas, were analyzed for microsatellite variation. The comparison group for our analysis, representing healthy individuals, consisted of 249 females which were exome sequenced as part of the 1,000 Genomes Project. We applied our microsatellite-based genotyping pipeline to identify 55 microsatellite loci that can distinguish between the germline of individuals diagnosed with breast cancer and healthy individuals with a sensitivity of 88.4 % and a specificity of 77.1 %. Further, we identified additional microsatellite loci that are potentially useful for distinguishing between breast cancer subtypes, revealing a possible fifth subtype. These findings are of clinical interest as possible risk diagnostics and reveal genes that may be of potential therapeutic value, including genes previously not associated with breast cancer.