?腫瘤樣本的鏡檢結(jié)果不是總能預(yù)測(cè)腫瘤的侵蝕性，使用有針對(duì)性的分子手段可以增加診斷的正確性,。目前,，哈佛大學(xué)麻省理工學(xué)院分部健康科學(xué)與技術(shù)CHIP的研究人員報(bào)道,，遺傳模式預(yù)測(cè)了染色體的不穩(wěn)定,，這種不穩(wěn)定性增加了染色體畸變的趨勢(shì),，是腫瘤發(fā)展的關(guān)鍵，也是多種腫瘤臨床的前兆,。
??從以前研究的18例腫瘤（有代表性的6種腫瘤）基因表達(dá)的結(jié)果來(lái)看,，在研究的種群中有12例的遺傳模式或遺傳標(biāo)記預(yù)示了不好的臨床結(jié)果。
??“染色體的不穩(wěn)定性是癌細(xì)胞增殖的一個(gè)關(guān)鍵機(jī)制,，” CHIP研究者與高級(jí)調(diào)查員Zoltan Szallasi說(shuō),，“我們通過(guò)檢測(cè)染色體的不穩(wěn)定性為可能的腫瘤樣本診斷提供了一個(gè)相對(duì)簡(jiǎn)單的途徑,。”
??這項(xiàng)技術(shù)有助于通過(guò)降低染色體的不穩(wěn)定性來(lái)開(kāi)發(fā)癌癥藥物----一種研究者很感興趣的方法---很可能篩選到大量有效藥物，Szallasi注解說(shuō),。為了很好的發(fā)展,，團(tuán)隊(duì)也可以形成用于臨床診斷的工具。
??由于環(huán)境的惡化,，人類(lèi)基因組有突變的危險(xiǎn),，基因復(fù)制中的錯(cuò)配，引起同源染色體的斷裂,，DNA 的丟失，重復(fù)和重組等的因素都會(huì)帶來(lái)錯(cuò)誤的染色體,。細(xì)胞有不斷修復(fù)這些破壞的機(jī)制,，但一旦修復(fù)機(jī)制被破壞，染色體就變得不穩(wěn)定,，癌疹就有可能發(fā)生,。
??染色體的不穩(wěn)定就會(huì)導(dǎo)致非整倍體的發(fā)生，這樣DNA的記憶單位就會(huì)丟失或重復(fù),。Szallasi團(tuán)隊(duì)發(fā)展的這項(xiàng)技術(shù)間接檢測(cè)了非整倍體的程度,，也就是通過(guò)檢測(cè)染色體不同位點(diǎn)基因異常表達(dá)的程度來(lái)判斷染色體不穩(wěn)定性的程度。
??另外,，研究者鑒定了能夠很好反映自身染色體不穩(wěn)定性的25個(gè)基因,。這些基因的標(biāo)記是各種腫瘤（乳腺癌，肺癌,，髓母細(xì)胞瘤,，神經(jīng)膠質(zhì)瘤，間皮瘤,，淋巴瘤）有意義的預(yù)報(bào)器,。他也可能在原發(fā)性腫瘤和腫瘤轉(zhuǎn)移灶之間分化，在各級(jí)腫瘤中,，一級(jí)和二級(jí)乳腺癌的侵蝕性表現(xiàn)得最明顯,。
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.
更多原文鏈接：http://www.eurekalert.org/pub_releases/2006-08/chb-oc081706.php
