文章：

FRA3B和其他常见的脆弱位点：最薄弱的环节

FRA3B and other common fragile sites: the weakest links

原文发布日期：2001-12-01

DOI: 10.1038/35106058

类型: Review Article

开放获取: 否

要点：

1. Common fragile sites occur on every human chromosome and are frequently involved in chromosome rearrangements in cancer. There might be genes at these fragile sites that contribute to the development of cancer.
2. There are more than 80 common fragile sites, meaning that we all have these weak links in our chromosomes, although there might be variations in the degrees of fragility among individuals.
3. Common fragile sites can be damaged by exposure to carcinogens, such as those in tobacco smoke. The damage to at least one fragile site — FRA3B — also damages the FHIT gene, which encompasses FRA3B.
4. Damage to FHIT contributes to the growth of cancer cells in the lung, kidney, stomach, bladder and other cancers.
5. Mice that are missing one or both Fhit genes are very susceptible to carcinogen-induced cancers that can be prevented or delayed by treatment with viral vectors carrying the FHIT gene.
6. The WWOX gene at FRA16D is also susceptible to DNA damage, causing alteration of expression of WWOX. Alteration of WWOX expression probably contributes to growth of breast, ovarian and other cancers.
7. Genes at other common fragile sites might also contribute to cancer and should be isolated and studied to uncover their functions in neoplastic disease.
8. It is likely that carcinogen exposure can damage several fragile genes within a single cell, thereby activating one or more oncogenes and inactivating one or more tumour-suppressor genes simultaneously.
9. Deletions, amplifications and translocations at fragile sites are a result of delayed replication by carcinogens or other chemicals within the fragile regions, but there is still much to learn about the induction of fragility, repair or misrepair of the damage, and the consequences to the genes in fragile regions.
10. The functions of the fragile genes FRA3B and WWOX are largely unknown.

要点翻译：

1. 常见脆性位点存在于每一条人类染色体上，并频繁参与癌症中的染色体重排。这些脆性位点可能存在某些基因，它们会促进癌症的发展。
2. 目前已知80多个常见脆性位点，这意味着我们所有人的染色体上都存在这些脆弱连接，尽管个体间的脆弱程度可能存在差异。
3. 常见脆性位点可能因接触致癌物（如烟草烟雾中的物质）而受损。至少有一个脆性位点——FRA3B——的损伤会同时破坏包含该位点的FHIT基因。
4. FHIT基因的损伤会促进肺癌、肾癌、胃癌、膀胱癌及其他癌症中癌细胞的生长。
5. 缺失一个或两个Fhit基因的小鼠对致癌物诱导的癌症非常敏感，而通过携带FHIT基因的病毒载体进行治疗可预防或延缓此类癌症。
6. FRA16D位点的WWOX基因同样易受DNA损伤影响，导致其表达改变。WWOX表达的改变可能会促进乳腺癌、卵巢癌及其他癌症的生长。
7. 其他常见脆性位点的基因也可能促进癌症发展，应通过分离和研究来揭示它们在肿瘤性疾病中的功能。
8. 致癌物暴露很可能损伤单个细胞内的多个脆性基因，从而同时激活一个或多个癌基因并灭活一个或多个抑癌基因。
9. 脆性位点的缺失、扩增和易位是致癌物或其他化学物质在脆弱区域内导致复制延迟的结果，但关于脆性诱导、损伤修复或错误修复以及脆性区域基因所受影响的机制仍有待深入研究。
10. 脆性基因FRA3B和WWOX的功能目前很大程度上仍属未知。

英文摘要：

In 1979, the first chromosome alteration associated with familial cancer was reported. Five years later, a fragile site was observed in the same chromosome region. The product of the fragile histidine triad (FHIT) gene, which encompasses this fragile site, is partially or entirely lost in most human cancers, indicating that it has a tumour-suppressor function. Inactivation of only one FHIT allele compromises this suppressor function, indicating that a 'one-hit' mechanism of tumorigenesis is operative. Are genes disrupted at other fragile sites? And, are these genes also tumour suppressors?

摘要翻译： 

1979年，首次报道了与家族性癌症相关的染色体改变。五年后，在同一染色体区域观察到一个脆性位点。脆性组氨酸三联体（FHIT）基因的产物覆盖了这一脆性位点，在大多数人类癌症中部分或完全缺失，表明其具有抑癌功能。仅失活一个FHIT等位基因就会损害这种抑制功能，说明存在“一次打击”的肿瘤发生机制。其他脆性位点上的基因是否也会被打断？这些基因是否也是肿瘤抑制因子？

原文链接：

FRA3B and other common fragile sites: the weakest links