Cancer genes decoded

6 Nov 2008

Researchers at the Genome Sequencing Center at Washington University in St. Louis have decoded the genes of a person with acute myeloid leukaemia and found a set of mutations that might have caused or aided the progression of the disease.

Using the cells from the patient who died of leukaemia, the DNA from the cancer cells was sequenced and compared to the DNA from normal, healthy skin cells from the same individual. The researchers chose to study acute myeloid leukaemia because it is severe and the treatment has not improved in decades.

Before starting treatment, the patient studied had donated samples of bone marrow and skin, so the researchers could compare her normal skin cells to cancer cells from her bone marrow.

They have identified 10 mutations present in the cancer cells, not present in the normal cells. Two are well-known AML-associated mutations, while the other eight mutations have not previously been detected in an AML genome. These mutations act to either stimulate abnormal growth, evade the bodies anti-cancer surveillance systems or make the cancer cells resistant to chemotherapeutic agents.

The importance of these mutations is that they could help in predicting the course of the disease or selecting treatments.

The mutations identified were not inborn, but developed later in life, like most mutations that cause cancer. Only a fraction of all cancers are thought to be hereditary.

The study, published this week in Nature (Nature 456, 66-72 (6 November 2008) | doi:10.1038/nature07485) aimed to find all the mutations involved in a particular cancer as opposed to earlier studies, which have looked at genes already suspected of being involved in the disease. The importance of this work is that it allows the identification of genes not already thought to be involved in cancer and would normally be missed. Indeed, 8 of the 10 mutations discovered would not have been found with the more traditional approach.

This next-generation, whole-genome approach, using the Illumina Genome Analyser, should allow the identification of new candidate genes that may be relevant for the pathogenesis of other types of cancer as well as leukaemia.

These findings could lead to new therapies and would almost certainly help doctors make better treatment choices based on a more detailed genetic picture of each patient’s cancer.

Most cancers are thought to begin in a single cell, with a mutation that is not present at birth but that occurs later for some unknown reason. Generally, one mutation is not enough to cause cancer and the disease will only develop when other successive mutations occur.

Some of the mutated genes appear to promote cancer growth. One probably made the cancer drug-resistant by enabling the tumour cells to pump chemotherapy drugs right out of the cell before they could do their work. The other mutated genes seemed to be tumour suppressors, the body’s natural defence against dangerous genetic mistakes.