Scientists from the Institute of Cancer Research say they have tracked the first mutations of leukaemia back to the mother’s womb, which they believe could lead to a target for new cancer drugs.
The study, which was published yesterday in the scientific journal PNAS, sequenced and analysed the entire 3bn letter genome of two pairs of identical twins with leukaemia to identify mutations driving the disease in the womb and post birth.
The twins had the most common form of leukaemia to affect children, acute lymphoblastic leukaemia (ALL), which is cancer of the white blood cells.
Leukaemia is the most common cancer diagnosed in children, killing 100 children a year in the UK. The disease is curable but often the treatment process is very uncomfortable and can cause extreme side effects.
Scientists decided to study identical twins because they often develop the cancer at the same time, suggesting shared genetic or environmental factors.
"It’s unusual in cancer to be able to identify the mutation that kick starts the whole process. Twin children, uniquely, provide an insight into the silent beginnings of leukaemia," said study co-author Professor Mel Greaves, professor of cell biology at The Institute of Cancer Research.
Greaves added that the implication of these new findings is that the first or ‘founder’ mutation might be able to provide an appropriate target for therapy as it is present in every cancer cell, unlike other mutations.
The research team collected genetic samples from the two sets of twins, both of whom developed ALL around the age of 4, and found a common leukaemia causing gene, which is generated in the womb by the exchange of genetic material between chromosomes.
They concluded that this gene must have been the critical ‘initiating’ genetic change leading to the twins developing leukaemia.
They believe the mutation arises in one cell in one twin, with cells carrying the mutation then spreading to the other twin via their shared circulation in the womb.
Out of the other 22 mutations shown in the two identical twins, no others were shared by both twins and therefore must have accumulated after birth as the disease progressed.
Three other chromosome changes were identified in both twins, which the scientists believe occurred in utero from the same single clone of cells.
The Institute of Cancer Research professor of molecular and population genetics and study co-author Professor Richard Houlston said; "This study helps us to better understand how leukaemia develops in utero, and provides us with promising new avenues for treatment."
Leukaemia & Lymphoma Research research director Professor Chris Bunce said; "Although the study was performed in young twins, it reveals processes that are relevant to adult leukaemias, which are far more common, and also potentially relevant to other cancers."
The research is largely funded by Leukaemia & Lymphoma Research, but has also received funding from the Kay Kendall Leukaemia Fund and Cancer Research UK
Image: Leukaemia kills around 100 children a year in the UK.
