Saxena Ajit Kumar
Cytogenetic & Molecular Genetic Laboratory, Centre of Experimental Medicine and Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India.
J Exp Ther Oncol. 2012;10(1):19-29.
Genomic integrity of the cancer cell is doubt-full because of fragility on chromosome. Fragile--sites are non-randomly distributed on human genome prone to form gaps or breaks at either pre/or metaphase chromosome arise when cells are exposed to a perturbation of DNA replication process. Cancer cells commonly show various form of "hot spots" including point mutation, chromosome copy number and translocation involving specific gene mutation but the genetic diversity of fragile sites are still not clear. The chromosomal fragile sites (rare & common fragile sites) make the cancer cells not only susceptible to genomic instability but also contribute the process of malignancy due to expansions of microsatellite CGG or AT rich minisatellite. Fragile sites have been implicated due to inter chromosomal amplification events by initiation breakage - fusion cycles. The mechanisms behind these changes give raise to new insight the cytogenetic manifestation of oncogenesis. Fragile sites loci are associated with activation of oncogenesis during cell--cycle analysis. However, these mutations at fragile sites loci might have play a causative or functional role in tumor biology. The topography organization and informatics complexity of the fragile sites remained unexplored due to lack of systematic approach towards molecular cloning of the fragile sites DNA sequences and specific models as not are under taken. The information regarding mode of inheritance of fragile sites are still lacking but the first degree relative specially young proband and maternal side having variable prevalence in different population could be uses as suitable marker for determining genetic predisposition to cancer. This comprehensive review of fragile sites in tumor biology probably helpful to explore to understand the molecular mechanism of carcinogenesis or tumorgenesis.
由于染色体的脆弱性,癌细胞的基因组完整性令人怀疑。脆性位点在人类基因组上非随机分布,当细胞暴露于DNA复制过程的扰动时,在前期或中期染色体上容易形成间隙或断裂。癌细胞通常表现出各种形式的“热点”,包括点突变、染色体拷贝数和涉及特定基因突变的易位,但脆性位点的遗传多样性仍不清楚。染色体脆性位点(罕见和常见脆性位点)不仅使癌细胞易受基因组不稳定的影响,而且由于微卫星CGG或富含AT的小卫星的扩增,也促进了恶性肿瘤的发生过程。由于起始断裂-融合循环导致的染色体间扩增事件,脆性位点也被牵连其中。这些变化背后的机制为肿瘤发生的细胞遗传学表现提供了新的见解。在细胞周期分析中,脆性位点基因座与肿瘤发生的激活有关。然而,这些脆性位点基因座的突变可能在肿瘤生物学中发挥了致病或功能作用。由于缺乏对脆性位点DNA序列进行分子克隆的系统方法,且未采用特定模型,脆性位点的拓扑结构组织和信息复杂性仍未得到探索。关于脆性位点遗传方式的信息仍然缺乏,但一级亲属,特别是年轻的先证者和母系在不同人群中具有不同的患病率,可作为确定癌症遗传易感性的合适标记。这篇关于肿瘤生物学中脆性位点的综合综述可能有助于探索理解致癌或肿瘤发生的分子机制。