Navigation Links
'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.

Source:Children's Hospital Boston

Related biology news :

1. Found: Missing sequence of the human Y chromosome
2. Variation in womens X chromosomes may explain differences among individuals, between sexes
3. Scientists analyze chromosomes 2 and 4
4. Normal chromosome ends elicit a limited DNA damage response
5. Utah researchers confirm chromosome may harbor autism gene
6. Mouse to man: The story of chromosomes
7. Movement of chromosome in nucleus visualized
8. Sex chromosome genes influence aggression andmaternal behavior, say UVa researchers
9. Researchers use multiphoton microscopy to watch chromosomes in action
10. Short chromosomes put cancer cells in forced rest
11. Researchers attach genes to minichromosomes in maize

Post Your Comments:

(Date:11/11/2015)... Minn. , Nov. 11, 2015   MedNet Solutions ... entire spectrum of clinical research, is pleased to announce that ... in Clinical Trials (PCT) event, to be held November ... be able to view live demonstrations of iMedNet ... and learn how iMedNet has been able to ...
(Date:11/9/2015)... , Nov. 09, 2015 ... addition of the "Global Law Enforcement ... offering. --> ) has ... Law Enforcement Biometrics Market 2015-2019" report ... and Markets ( ) has announced ...
(Date:11/2/2015)... Calif. , Nov. 2, 2015  SRI International ... million to provide preclinical development services to the National ... contract, SRI will provide scientific expertise, modern testing and ... variety of preclinical pharmacology and toxicology studies to evaluate ... --> The PREVENT Cancer Drug Development Program ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... , ... November 25, 2015 , ... ... uBiome, were featured on AngelList early in their initial angel funding process. Now, ... syndicate for individuals looking to make early stage investments in the microbiome space. ...
(Date:11/24/2015)... 2015 /CNW/ - iCo Therapeutics ("iCo" or "the Company") ... for the quarter ended September 30, 2015. Amounts, ... and presented under International Financial Reporting Standards ("IFRS"). ... said Andrew Rae , President & CEO ... not only value enriching for this clinical program, ...
(Date:11/24/2015)... PUNE, India , November 24, 2015 ... to a new market research report "Oligonucleotide Synthesis Market ... Equipment), Application (PCR, Gene Synthesis, Diagnostic, DNA, RNAi), End-User ... to 2020", published by MarketsandMarkets, the market is expected ... 1,078.1 Million in 2015, at a CAGR of 10.1% ...
(Date:11/24/2015)...  Tikcro Technologies Ltd. (OTCQB: TIKRF) today announced that its Annual General ... a.m. Israel time, at the law offices of ... 36 th Floor, Tel Aviv, Israel . ... Izhak Tamir to the Board of Directors; , election ... , approval of an amendment to certain terms of options granted to ...
Breaking Biology Technology: