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Scientists uncover cause of common cancer chromosome defect

Friday 19 August 2011

The absence of a specific gene could lead to cells being more likely to develop into cancer, according to US scientists

US researchers have found that a gene called STAG2 is commonly faulty or missing in several types of cancer, and that this causes cells to have an abnormal number of chromosomes - a frequent sign of cancer.

Healthy cells contain 23 pairs of chromosomes, which hold their DNA code. But cancer cells often contain more or fewer than this. Until now, it wasn't known if this abnormal chromosome number - called aneuploidy - was a cause or consequence of the disease.

In new research, published in the journal Science, scientists at the Georgetown University Medical Center showed that one in five brain, skin and bone cancer samples tested were not able to produce STAG2 protein, often because the gene that codes for the protein was missing or mutated.

Previous research has shown that STAG2 has an important role in controlling the separation of chromosomes during cell division, but researchers didn't know if this was linked to cancer.

The researchers now believe that when the STAG2 gene is inactive, dividing cells are more likely to produce 'daughter' cells with an abnormal number of chromosomes.

This means the new cells either have too few or too many genes, making them significantly more likely to develop into cancer.

Lead author Dr David Solomon hopes that the study could provide the basis for a new direction in cancer therapy.

He said: "We are now attempting to identify a drug that specifically kills cancer cells with STAG2 mutations. Such a drug would be of clinical benefit to the many patients whose tumours have inactivation of STAG2."

Dr Julie Sharp, senior science information manager at Cancer Research UK, said: "Scientists have known for more than 100 years that having too many or too few chromosomes is linked to cancer and these results suggest that this is not just a characteristic but a cause of the disease.

"Their discovery sheds light on how chromosome numbers can be altered when cells divide and presents researchers with new ways to tackle cancer by designing drugs to upset this chain of events."

Solomon, D., Kim, T., Diaz-Martinez, L., Fair, J., Elkahloun, A., Harris, B., Toretsky, J., Rosenberg, S., Shukla, N., Ladanyi, M., Samuels, Y., James, C., Yu, H., Kim, J., & Waldman, T. (2011). Mutational Inactivation of STAG2 Causes Aneuploidy in Human Cancer Science, 333 (6045), 1039-1043 DOI: 10.1126/science.1203619