The root genetic cause of leukaemia has been traced back to early life in the womb, scientists say.
Experts from the Institute of Cancer Research in London, UK, analyzed the entire three billion letter sequence of DNA-coding in identical twins to reveal what sets off the disease.
Researchers hope the findings, published in PNAS journal, could lead to new drugs to fight the condition at source.
Leukaemia is the most common cancer diagnosed in children.
The root genetic cause of leukaemia has been traced back to early life in the womb
Researchers studied twins studied that had the most common form of leukaemia that affects children – acute lymphoblastic leukaemia (ALL), which is a cancer of the white blood cells.
It is already known that multiple faulty genes are linked to the condition and that environmental factors probably act as triggers along the way. But the precise sequence of events leading up to a diagnosis of ALL is unclear.
The scientists wanted to find out more about the disease so that, ultimately, a better treatment could be found.
Although ALL is often curable, the medicines used to treat it can cause unpleasant and sometimes severe side effects.
Prof. Mel Greaves and his colleagues decided to study identical twins who shared the same DNA inherited from their parents.
Both twins developed ALL in early childhood, at around four years of age.
By comparing blood and bone marrow samples of the twins in later childhood, the researchers found one genetic mutation identical in both twins – a common leukaemia-causing gene called ETV6-RUNX1.
The scientists reason that this mutation must have arisen in one of the twins while in the womb.
Cells carrying the mutation then spread to the other twin via their shared placental blood circulation.
The identical twins had a total of 22 other mutations, but none of these mutations was shared by both twins, and so they must have accumulated after birth as the disease progressed, say the researchers.
Study co-author Prof. Mel Greaves said: “We were able to sequence the entire human genome. It told us for the first time that this is the key mutation that starts the whole process of leukaemia. The other mutations must have happened after birth.”
Denmark has decided to tighten the rules of sperm donation after one donor was found to have passed on a rare genetic condition to at least five of the 43 babies he is thought to have fathered.
Neurofibromatosis type 1 (NF1) produces tumors that affect the nervous system, and the affected sperm is thought to have been used in 10 countries.
The sperm bank has been criticized for failing to screen for the condition.
Donors will now only be allowed to donate enough for 12 inseminations.
Denmark has liberal sperm donation policies that appeal to women who want to conceive using artificial insemination.
Denmark has liberal sperm donation policies that appeal to women who want to conceive using artificial insemination
The Copenhagen sperm bank Nordisk Cryobank said it was aware of five babies that had been born with NF1.
The clinic’s director, Peter Bower, told Agence France-Presse that confidentiality rules meant he was unable to give detail on how old the children were, or where they lived.
But he said the donor was known to have provided sperm to women prior to October 2008, in countries inside and outside Europe.
He said Nordisk Cryobank did not stop using the sperm immediately because it could not be sure the donor was responsible for passing on the condition.
The donated sperm was used by 14 different fertility clinics, Danish broadcaster DR reports.
NF1 is caused by a genetic mutation. In half of all cases it is passed from a parent to their child. In other cases, the mutation develops on its own.
It can produce a wide range of symptoms – from unusual skin pigmentation, to serious and disfiguring non-cancerous tumors which can sometimes turn cancerous.
It can also cause learning difficulties, problems with vision, and an abnormally curved spine.
There is no treatment for the condition, but the symptoms can be managed.
A mother of one of the affected children, Mia Levring, condemned the clinic’s actions, saying she was “shaken and shocked”.
Another, Sonja Pedersen, said: “We are dealing with a lot of children, but there is also the economical aspect. They earn a lot of money doing this. And one has a responsibility to make sure that the product, so to speak, is all right.”
The head of the Danish Health and Medicines Authority, Anne-Marie Vangsted, criticized the sperm bank, saying it had failed to withdraw the sperm when it first became aware of the problem.
It is unclear how the donor who passed on NF1 was able to father 43 children, despite Denmark’s current limit of 25.
The new limit of 12 will be introduced from 1 October.
