Page URL:

Common cancer gene may change chromosome numbers

22 August 2011
Appeared in BioNews 621

Two US studies published this week have shed light on how a gene mutation can change the number of chromosomes present in the cells of more than 90 percent of cancers.

The first study, led by the Lombardi Comprehensive Cancer Center at Georgetown University School of Medicine (GUSM) in Washington, DC, has identified that STAG2 - a commonly mutated gene in cancer - is directly involved in causing aneuploidy. The second study, led by the researchers at the Massachusetts Institute of Technology (MIT), has shown that aneuploidy causes genetic instability that can pave the way for malignant tumour growth and other cancerous defects. Together the studies have opened up an avenue for research that could lead to new drugs for people with cancer, which target cells containing the mutation.

Aneuploidy is found in almost all cancers, but the phenomenon was poorly understood because it was unclear whether it was a cause or effect of cancer. The studies, reported in Science, show that it is a bit of both.

The STAG2 gene influences the production of a protein structure called the 'cohesin complex', which regulates how chromosomes are separated during cell division. Mutations in STAG2 mean that cells are more likely to have uneven numbers of chromosomes after division, leading to an increased risk that they will develop into cancer cells.

The GUSM study found that in 20 percent of the cancer cells they studied, including types of brain, skin and bone cancer, the STAG2 gene was missing or mutated. The team then manipulated tumour cell lines to repair and induce STAG2 mutations, with the number of chromosomes becoming more stable when it was repaired and less stable when it was mutated. The findings suggest the mutation is a 'first step' toward normal cells transforming into cancer cells.

The MIT study examined the effects of aneuploidy on the functioning of the cell. The team was able to determine that the mutation increases the chances of disruption in genome repair and maintenance, because the cell struggles to maintain genome function when there are extra chromosomes.

Associate Professor Todd Waldman, senior author on the GUSM study, said: 'When cells are in a state of aneuploidy, their mitotic machinery gets somewhat confused by the abnormal chromosome count and that perpetuates the instability'.

The latter findings are based on yeast cells and it is not yet clear whether human cells respond in the same way to genomic instability. But the study, if replicated in human cells, could have huge implications. 'The grand implication is that mutation of one single gene can be responsible for all sorts of instability seen in tumors', said Duane Compton, Professor of Biochemistry at Dartmouth Medical School in New Hampshire who was not involved in the study.

Aneuploidy Drives Genomic Instability in Yeast
Science |  19 August 2011
Chromosomes and Cancer
The Scientist |  18 August 2011
Mutant gene identified that causes abnormal chromosome count, leading to cancer
Eurekalert |  18 August 2011
Mutational Inactivation of STAG2 Causes Aneuploidy in Human Cancer
Science |  19 August 2011
Three cancers share genetic link
BBC News |  19 August 2011
5 December 2011 - by Dr Zara Mahmoud 
Two new gene variants, which each increase the risk of bone marrow cancer by 30 percent, have been identified by scientists at the Institute for Cancer Research...
8 August 2011 - by Sarah Pritchard 
Genetic differences between two types of stomach cancer could help doctors select the most effective treatment for a patient's tumour, say Singapore researchers. The research team used a new, better method of classifying tumours to distinguish 'diffuse' from 'intestinal' tumours....
4 July 2011 - by Dr Lux Fatimathas 
European researchers have linked ovarian stimulation in women aged over 35 to increased chromosomal abnormalities. Genetic screening shows that the production of oocytes is disrupted during fertility treatment involving ovarian stimulation...
20 June 2011 - by Dr Susan Kelly 
The world of genetically predicted futures has recently been joined by a test for what is advertised as ‘biological age’. The test promises to provide information about the rate at which one is ageing – and knowing when you will die would make planning for the future so much easier!...
6 June 2011 - by Dr Rachael Panizzo 
Scientists have identified a set of 15 genes that are associated with triple-negative breast cancer (TNBC), an aggressive form of the disease that does not respond to the drugs commonly used to treat other types of breast cancer...
to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions

Syndicate this story - click here to enquire about using this story.