Microsatellite Sequencing to Enable Cancer Genotyping

项目摘要 电子生物科学(EBS)将研究和开发精确测序微卫星的方法 人类基因组中的区域，以实现癌症基因分型。微卫星是简单/短重复序列(1-10 长度上的核苷酸)串联出现5-50次，并且是最可变的DNA序列类型 在基因组中。这些微卫星区域的突变包括重复数的扩大或收缩， 单核苷酸多态(SNPs)和/或插入或缺失(Indels)，已有文献记载 癌症的易感性、癌症的发病和/或多种癌症的预后，包括结肠癌、乳腺癌、 膀胱、脑、头颈部、皮肤、甲状腺、肾脏、前列腺、肺、卵巢和肝脏。然而，到目前为止，有 目前还没有完全适用于微卫星测序/表征的技术， 极大地限制了对微卫星突变和相关疾病的发展的了解 诊断/预后分析。在这个为期两年的计划中，EBS将专注于开发方法来 通过直接的、电子的、基于纳米孔的、 单分子测序。在该计划期间进行的调查将使新的方法能够 以前所未有的细节探测人类基因组，以便关联和统计微卫星 表示特定癌症类型、易感性、发病和/或预后的序列，直接改善基本 癌症研究，并最终改进临床诊断和/或预后技术。

Project Summary Electronic BioSciences (EBS) will investigate and develop methodologies to accurately sequence microsatellite regions within the human genome to enable cancer genotyping. Microsatellites are simple/short repeats (1-10 nucleotides in length) that occur in tandem 5-50 times, and are among the most variable types of DNA sequence in the genome. Mutations to these microsatellite regions include expansion or contraction of the repeat number, single nucleotide polymorphisms (SNPs), and/or insertions or deletions (indels), which have been documented with cancer predisposition, cancer onset, and/or prognosis for many types of cancer, including colon, breast, bladder, brain, head and neck, skin, thyroid, kidney, prostate, lung, ovarian, and liver. To date, however, there is no technology presently available that is ideally suited for microsatellite sequencing/characterization, which has significantly limited the understanding of microsatellite mutations and the development of associated diagnostic/prognostic assays. During this two-year program, EBS will focus on developing the methodology to sequence and genotype microsatellites from colon cancer cell lines via direct, electronic, nanopore-based, single-molecule sequencing. The investigations performed during this program will enable new approaches to probe the human genome with unprecedented detail in order to relate and statistically characterize microsatellite sequences that signify a specific cancer type, predisposition, onset, and/or prognosis, directly improving basic cancer research and enabling eventual improved clinical diagnostics and/or prognostics technologies.