October 13, 2009 -- A woman suffering from cancer during pregnancy can pass the disease on to her unborn child, scientists have shown in a study that solves a puzzle that has perplexed doctors for a century. The rare occurrence of a mother and child appearing to share the same cancer — of which there have been about 30 known cases — is a result of a genetic mutation that allows the cancer to pass to the baby undetected. The scenario has baffled scientists by defying accepted theories of biology that suggest that even if a cancer were able to cross the placental barrier, it would be rejected by the baby’s immune system. There was previously no genetic evidence to explain why a child’s immune system would not recognise and destroy any invasive cancer cells that were of maternal — and therefore, foreign — origin.

The new study, led by Mel Greaves, of the Institute of Cancer Research (ICR), and published in Proceedings of the National Academy of Sciences, used advanced genetic fingerprinting to prove that an infant’s leukaemic cells were unquestionably of maternal origin. The case, involving a Japanese mother aged 28 and her daughter, revealed that both patients’ leukaemic cells carried the identical mutated cancer gene BCR-ABL1 even though the infant had not inherited this gene. This meant that the child, who had cancer diagnosed at 11 months old, could not have developed this type of leukaemia in isolation.

To investigate how the cells could have crossed the placental barrier and survived in the offspring the scientists looked for evidence of some form of immunological acceptance or tolerance of the foreign cells by the foetus. They examined the genes of the cancer cells in the infant and found a deletion mutation — some DNA missing in the region that acts to distinguish one individual and his or her cells from another. The absence of these molecules on the cancer cells meant that the infant’s immune system would not have recognised that they were foreign.

Professor Greaves, who worked with colleagues in Japan with funding from Leukaemia Research, said that it had been assumed that cancer spread was impossible because of the placenta’s role in preserving materno-foetal health. “The placenta is a very effective barrier for maternal health, otherwise mother would reject baby,” he said. “It would follow that even if a very few cells would get across surely baby would deal with them. But this shows that [the mutation] can affect that critical recognition of one human from the next. It may happen more often than we expect.” Professor Greaves said that melanoma and leukaemia were likely candidates for spread. “Melanoma has an extraordinary proclivity to metastasise in the body and leukaemia [as a blood cancer] naturally infiltrates too.”

The mother, who had leukaemia diagnosed after giving birth, died a few weeks later last year. The baby girl, who developed a jaw tumour that was shown to carry the same genetic markers as the mother’s cancer, has been treated intensively and is doing well, Professor Greaves added.

Rare cases
• It was reported in 1999 that a mother in the U.S. might have passed lymphoma to her foetus. She died 18 days after her son was delivered. He also died

• One review suggested 19 cases of skin cancer that had spread to the placenta; 5 spread to the foetus