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Identical twin genome study reveals leukaemia's embryonic origins

15 April 2013
Appeared in BioNews 700

Genome analysis of identical twins with childhood leukaemia has helped pinpoint genetic mutations which may kick-start the disease in the mother's womb.

Study co-author Mel Greaves, professor of cell biology at the Institute of Cancer Research, said that being able to identify such genes was 'unusual' but that 'twin children, uniquely, provide an insight into the silent beginnings of leukaemia'.

The study, published in the journal PNAS, focused on two pairs of twins with acute lymphoblastic leukaemia (ALL), the most common childhood cancer.

Scientists took blood and bone marrow samples from the twins. After sequencing their genomes, researchers found that one pair of twins had a total of 23 mutations. However, the only mutation shared by both children was in the common leukaemia-causing gene ETV6-RUNX1.

The researchers reason that this must have been the critical 'founder' mutation leading to development of the disease. They suggest that the faulty gene must have originated in one twin before mutated cells then spread to the sibling via the shared placental blood supply in the womb. The 22 other mutations are thought to have arisen as the disease developed after birth.

In the other pair of identical twins, both children were found to have inherited a mutation called NF1, predisposing them to a condition called neurofibromatosis - a major risk factor for leukaemia. Three other chromosome changes were identified in both twins, which the scientists believe occurred early on in utero before the fertilised egg cell split.

Professor Greaves said that one implication of the study was 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'.

Dr Julie Sharp of Cancer Research UK, which helped fund the study, added: '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'.

ALL is an aggressive cancer of the white blood cells which primarily affects children. Although it is curable in 80 to 90 percent of cases, current treatments have serious side effects.

Developmental timing of mutations revealed by whole-genome sequencing of twins with acute lymphoblastic leukemia
PNAS |  8 April 2013
Identical twins' genes reveal the 'silent beginnings' of leukaemia
The Institute of Cancer Research (press release) |  8 April 2013
Leukemia Linked to Changes in Womb
The Scientist |  10 April 2013
Scientists track leukaemia's origins 'back to the womb'
BBC News |  9 April 2013
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