?肿瘤样本的镜检结果不是总能预测肿瘤的侵蚀性，使用有针对性的分子手段可以增加诊断的正确性。目前，哈佛大学麻省理工学院分部健康科学与技术CHIP的研究人员报道，遗传模式预测了染色体的不稳定，这种不稳定性增加了染色体畸变的趋势，是肿瘤发展的关键，也是多种肿瘤临床的前兆。
??从以前研究的18例肿瘤（有代表性的6种肿瘤）基因表达的结果来看，在研究的种群中有12例的遗传模式或遗传标记预示了不好的临床结果。
??“染色体的不稳定性是癌细胞增殖的一个关键机制，” CHIP研究者与高级调查员Zoltan Szallasi说，“我们通过检测染色体的不稳定性为可能的肿瘤样本诊断提供了一个相对简单的途径。”
??这项技术有助于通过降低染色体的不稳定性来开发癌症药物----一种研究者很感兴趣的方法---很可能筛选到大量有效药物，Szallasi注解说。为了很好的发展，团队也可以形成用于临床诊断的工具。
??由于环境的恶化，人类基因组有突变的危险，基因复制中的错配，引起同源染色体的断裂，DNA 的丢失，重复和重组等的因素都会带来错误的染色体。细胞有不断修复这些破坏的机制，但一旦修复机制被破坏，染色体就变得不稳定，癌疹就有可能发生。
??染色体的不稳定就会导致非整倍体的发生，这样DNA的记忆单位就会丢失或重复。Szallasi团队发展的这项技术间接检测了非整倍体的程度，也就是通过检测染色体不同位点基因异常表达的程度来判断染色体不稳定性的程度。
??另外，研究者鉴定了能够很好反映自身染色体不稳定性的25个基因。这些基因的标记是各种肿瘤（乳腺癌，肺癌，髓母细胞瘤，神经胶质瘤，间皮瘤，淋巴瘤）有意义的预报器。他也可能在原发性肿瘤和肿瘤转移灶之间分化，在各级肿瘤中，一级和二级乳腺癌的侵蚀性表现得最明显。
部分英文原文：
?'Signature' of chromosome instability predicts cancer outcomes
Microscopic examination of tumor specimens cannot always predict a cancer's aggressiveness, leading to increased interest in molecular approaches to diagnosis. Now, researchers in the Children's Hospital Informatics Program (CHIP) at the Harvard-MIT Division of Health Sciences and Technology report that a genetic profile indicating chromosomal instability -- an increased tendency to develop chromosomal aberrations, critical in cancer development -- is predictive of clinical outcome in a broad range of cancer types.
Using data on gene expression (activity) from 18 previous studies of cancer, representing six cancer types, they found that this genetic profile, or signature, predicted poor clinical outcome in 12 of the populations studied. The study was published online by the journal Nature Genetics on August 20.
"Chromosomal instability is one of the key mechanisms that keeps malignant cell proliferation going," says Zoltan Szallasi, MD, a CHIP researcher and the study's senior investigator. "We have achieved a relatively easy way to measure the level of chromosomal instability in a given tumor sample."
The technique may help in the search for cancer drugs that reduce chromosomal instability -- an approach of increasing interest to researchers -- by making it possible to screen a large number of drugs for efficacy, Szallasi notes. With further development, the team's work could also form the basis of a diagnostic tool that could be used in the clinic.
The human genome is at constant risk for mutations due to environmental insults, errors in gene replication, and other factors that can cause chromosomes to break and bits of DNA to be lost, duplicated or reshuffled to the wrong chromosomes. Cells have repair mechanisms that constantly fix this damage, but when the repair process breaks down, chromosomes become unstable and cancers are more likely to develop.
Chromosomal instability leads to a condition known as aneuploidy, in which chunks of DNA are either missing or duplicated. The technique developed by Szallasi's team indirectly measures the degree of aneuploidy -- and thus the degree of chromosomal instability -- by looking for abnormal expression levels of genes at the different chromosomal locations.
Next, the researchers identified 25 genes whose activity most strongly predicted chromosomal instability itself. This 25-gene signature was a significant predictor of clinical outcomes in a variety of cancers (breast, lung, medulloblastoma, glioma, mesothelioma and lymphoma). It could also differentiate between primary tumors and tumor metastases, and, in grade 1 and grade 2 breast cancer, distinguished the more aggressive cancers within each grade.
更多原文链接：http://www.eurekalert.org/pub_releases/2006-08/chb-oc081706.php
