The experts conducted their study at The Institute of Cancer Research, London, and published their findings in the journal Proceedings of the National Academy of Sciences (PNAS).
After examining two pairs of identical twins, the investigators discovered indicators of the emergence of leukemia in kids. These early genetic origins of childhood leukemia could help in the development of new treatments because they represent mutations that exist in every single cancer cell, which plays a critical part in the development of the disease.
Leukemia is the most prevalent cancer among children. One third of young cancer victims struggle with the disease, which kills 100 kids each year in the UK.
Leukemia generally develops in identical twin children at the same time, indicating shared genetic or environmental factors.
The researchers set out to examine this association by sequencing the entire 3 billion letter genome of identical twins with the disease. They wanted to find the mutations responsible for the cancer in the womb and after birth.
Professor Mel Greaves, study co-author and Professor of Cell Biology at The Institute of Cancer Research, said:
"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. One implication of these new findings is that the first or 'founder' mutation might provide an appropriate target for therapy as, unlike all subsequent mutations, it is present in every cancer cell."
Genetic samples were taken from two sets of identical twins who had acute lymphoblastic leukemia (ALL) - the most prevalent type of leukemia in kids.
ETV6-RUNX1 & NF1 mutations identifiedThe team discovered that the only notable mutation shared in two of the twins was ETV6-RUNX1, a common leukemia-causing gene that is generated in the womb by the trading of genetic material between chromosomes. Therefore, the authors believe that it must have been the first crucial genetic change causing their disease.
In one cell in one twin, the mutation emerges, with cells carrying the mutation and then spreading to the other twin through the circulation they share in the womb, the authors explained.
Twenty-two other mutations were expressed in the two identical twins, but none of them were found in both twins. This suggests that after they were born, they must have accumulated as the leukemia developed.
A mutation called NF1 was found in the second pair of identical twins, which was inherited from their parents. This made them susceptible to neurofibromatosis, a significant risk factor for leukemia.
Three other chromosome alterations were found in both twins, which probably happened in utero from the same single clone of cells.
Promising new paths for treatmentProfessor Richard Houlston, co-author and Professor of Molecular and Population Genetics at The Institute of Cancer Research, said:
"From a clinical perspective, it's very rare that you will get a set of identical twins with lymphoblastic leukemia, so to be able to sequence the whole genome of two pairs of twins with this disease is an important achievement. This study helps us to better understand how leukemia develops in utero, and provides us with promising new avenues for treatment."
"The research team at the ICR has been at the forefront of studies into leukaemia in twins that have developed a deeper understanding of the types and sequence of events that lead to blood cells becoming cancerous," Professor Chris Bunce, Research Director at Leukaemia & Lymphoma Research, said.
This research used advanced emerging technologies to better comprehend how cancer develops. Even though it involved young twins, it brings to light processes that are pertinent to leukemia in adults, which is much more common and also possibly associated with other cancers, Bunce added.
Dr Julie Sharp, Senior Science Information Manager at Cancer Research UK, concluded:
"This interesting research shows how studying the DNA of twins can shed light on the genetic mistakes that first initiate cancer in children and the subsequent faults that occur as the cancer evolves. Studies like this could reveal new ways to target the very roots of cancer and help us better understand how the disease develops over time. Survival rates have increased significantly over the past decades thanks to research, but there is still more to do to make treatments better with fewer side-effects."
A recent study showed that two kids with an aggressive form of childhood leukemia had a complete remission of their disease after treatment with a novel cell therapy, and a different report published earlier this year demonstrated that cell therapy may be effective for advanced leukemia in adults.
Written by Sarah Glynn