De Lellis L, Curia M C, Aceto G M, Toracchio S, Colucci G, Russo A, Mariani-Costantini R, Cama A
Department of Oncology and Neurosciences, G. D. Annunzio University Foundation, Chieti, Italy.
Ann Oncol. 2007 Jun;18 Suppl 6:vi173-8. doi: 10.1093/annonc/mdm251.
Screening for genomic rearrangements is a fundamental task in the genetic diagnosis of many inherited disorders including cancer-predisposing syndromes. Several methods were developed for analysis of structural genomic abnormalities, some are targeted to the analysis of one or few specific loci, others are designed to scan the whole genome. Locus-specific methods are used when the candidate loci responsible for the specific pathological condition are known. Whole-genome methods are used to discover loci bearing structural abnormalities when the disease-associated locus is unknown. Three main approaches have been employed for the analysis of locus-specific structural changes. The first two are based on probe hybridization and include cytogenetics and DNA blotting. The third approach is based on PCR amplification and includes microsatellite or single nucleotide polymorphism (SNP) genotyping, relative allele quantitation, real-time quantitative PCR, long PCR and multiplex PCR-based methods such as multiplex ligation-dependent probe amplification and the recently developed nonfluorescent multiplex PCR coupled to high-performance liquid chromatography analysis. Whole-genome methods include cytogenetic methods, array-comparative genomic hybridization, SNP array and other sequence-based methods. The goal of the present review is to provide an overview of the main features and advantages and limitations of methods for the screening of structural genomic abnormalities relevant to oncological research.
基因组重排筛查是许多遗传性疾病（包括癌症易感综合征）基因诊断中的一项基本任务。已开发出多种方法用于分析基因组结构异常，有些方法针对一个或几个特定基因座进行分析，其他方法则旨在扫描整个基因组。当已知导致特定病理状况的候选基因座时，使用基因座特异性方法。当疾病相关基因座未知时，使用全基因组方法来发现存在结构异常的基因座。已采用三种主要方法来分析基因座特异性结构变化。前两种基于探针杂交，包括细胞遗传学和DNA印迹法。第三种方法基于PCR扩增，包括微卫星或单核苷酸多态性（SNP）基因分型、相对等位基因定量、实时定量PCR、长PCR以及基于多重PCR的方法，如多重连接依赖性探针扩增和最近开发的与高效液相色谱分析相结合的非荧光多重PCR。全基因组方法包括细胞遗传学方法、阵列比较基因组杂交、SNP阵列和其他基于序列的方法。本综述的目的是概述与肿瘤学研究相关的结构基因组异常筛查方法的主要特点、优点和局限性。
