Genotype to phenotype: analyzing the effects of inherited mutations in colorectal cancer families.
Genotype to phenotype: analyzing the effects of inherited mutations in colorectal cancer families.
复制标题
DOI：
10.1016/j.mrfmmm.2009.09.004
复制
发表时间：
2010-11-10
影响因子：
2.3
通讯作者：
Heinen, Christopher D.
中科院分区：
文献类型：
--
作者：
Heinen, Christopher D.
关键词：
随着 DNA 测序技术的改进，包括对组织样本进行“深度测序”的大规模并行测序的出现，确定肿瘤中所有核苷酸变异的能力成为可能。这些信息将使我们能够更全面地了解每种肿瘤内的异质性，并识别与癌症发展有关的新基因。然而，出现的新挑战将是解释每个遗传变异的致病意义。通过关注遗传性结肠癌综合征、家族性腺瘤性息肉病 (FAP) 和遗传性非息肉病性大肠杆菌 (HNPCC) 所涉及的基因，可以证明这一挑战的艰巨性和复杂性。大约二十年前就确定了导致每种疾病的基因——FAP 的 APC 和 HNPCC 的 MMR 基因——并且在遗传性癌症患者的这些基因中发现了大量种系变异。然而，将个体基因型的影响与表型联系起来并不总是那么简单。本综述重点关注 APC 和 MMR 基因在肿瘤发展中的作用，以及为将每个基因中的不同变异与功能畸变和最终肿瘤发生联系起来所做的工作。通过考虑已经对两种具有明确遗传关联的明确疾病所做的工作，人们可以开始了解随着通过肿瘤测序发现新基因和基因突变而面临的挑战。
With improvements to DNA sequencing technologies, including the advent of massively parallel sequencing to perform “deep sequencing” of tissue samples, the ability to determine all of the nucleotide variations in a tumor becomes a possibility. This information will allow us to more fully understand the heterogeneity within each tumor, as well as to identify novel genes involved in cancer development. However, the new challenge that arises will be to interpret the pathogenic significance of each genetic variant. The enormity and complexity of this challenge can be demonstrated by focusing on just the genes involved in the hereditary colon cancer syndromes, familial adenomatous polyposis (FAP) and hereditary non-polyposis coli (HNPCC). The genes responsible for each disease were identified almost two decades ago -- APC for FAP and the MMR genes for HNPCC - and a large number of germline variations have been identified in these genes in hereditary cancer patients. However, relating the effect of an individual genotype to phenotype is not always straightforward. This review focuses on the roles of the APC and MMR genes in tumor development and the work that has been done to relate different variants in each gene to functional aberrations and ultimately tumorigenesis. By considering the work that has already been done on two well-defined diseases with clear genetic associations, one can begin to understand the challenges that lie ahead as new genes and gene mutations are discovered through tumor sequencing.
登录
查看更多内容
影响因子：
64.8
作者：
BRONNER, CE;BAKER, SM;LISKAY, RM
通讯作者：
LISKAY, RM
影响因子：
3.9
作者：
Chao, Elizabeth C.;Velasquez, Jonathan L.;Lipkin, Steven M.
通讯作者：
Lipkin, Steven M.
影响因子：
9.8
作者：
Berends, MJW;Wu, Y;Kleibeuker, JH
通讯作者：
Kleibeuker, JH
影响因子：
3.5
作者：
Albuquerque, C;Breukel, C;Smits, R
通讯作者：
Smits, R
影响因子：
64.8
作者：
BODMER, WF;BAILEY, CJ;SPURR, NK
通讯作者：
SPURR, NK