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Scientists tracked a specific gene fault from mother to baby

Scientists tracked a specific gene fault from mother to baby

One of the stories in the news today is the scientific proof that some cancers can, in some circumstances, spread from a mother to her baby while in the womb.

Before we look at the research in depth, the first thing to point out is that this is extremely rare. Since 1866, there have only been a handful of recorded cases of cancer spreading from a mother to her growing baby, so this isn’t something that pregnant women should worry about.

That said – if you have any concerns about cancer, you can call our Information Nurses on 0207 061 8355 or freephone 0808 800 4040.

Now let’s turn to the science behind this unusual story to see what happened, and – perhaps more importantly – why.

The case study

The story comes from a paper published in the journal Proceedings of the National Academy of Sciences, from researchers in the UK and Japan, led by Professors Mel Greaves and Shuki Mizutani. The paper describes the case of a 28-year old Japanese woman who gave birth to a healthy baby girl.

Everything seemed to be going well, until the woman suffered from bleeding and fever around a month after the birth. Tests revealed that she was suffering from a form of acute lymphoblastic leukaemia (ALL), and she began receiving treatment.

Sadly, 11 months later, the baby girl also started to show strange symptoms. She was taken to hospital with a tumour in her jaw and fluid leaking from her lungs (known as a pleural effusion).

Lab tests were carried out on samples of the tumour and the fluid, showing that the child also had cancer. Because of her symptoms, the doctors classified the cancer as a type of lymphoblastic lymphoma. But could it actually have been the same cancer that affected her mother?

What happened?
To find out, the researchers carried out detailed analysis of a specific gene fault – known as the BCR-ABL fusion gene, or the Philadelphia chromosome – which they had discovered in the mother’s cancer cells.

This fault is caused by two chromosomes (numbers 9 and 22) breaking and then fusing together, creating ‘hybrid’ chromosomes made from part of 9 and part of 22. The fusion is common in many leukaemias, but it happens at slightly different places every time. This means that individual cancers have unique DNA sequences at the points where the two chromosomes broke and rejoined.

But Greaves’ team found that the cancer samples from both the mother and child had identical DNA sequences around the break-point of their fused chromosomes. This couldn’t be a coincidence – the only explanation was that cancer cells from the mother had crossed the placenta and started growing in the developing baby.

Something still didn’t seem right. Although the placenta provides an effective barrier between the mother and child, we know that cells can still sneak across. But the baby’s immune system should have identified the cancer cells as being ‘foreign’, and destroyed them. Why didn’t it happen in this case?

Why did it happen?

To answer this question, the researchers looked again at the samples from the tumour in the child’s jaw, and at blood samples from the mother, father and child.

They found something very unusual. The rogue cancer cells that passed from mother to child were missing a crucial piece of DNA that would normally have alerted the child’s immune system to the presence of the invading cells.

This missing chunk contained genes for molecular ‘flags’ called MHC antigens that stick out from the surface of cells and communicate with our immune system. With it, the baby’s immune system would have recognised her mother’s leukaemia cells as foreign invaders and tried to destroy them. Without it, the cancer cells had effectively become ‘cloaked’, and were invisible to the immune system.

What does this case tell us?

Cases like this are very rare. As mentioned above, fewer than thirty cases have been published – mostly melanoma that has spread from mother to child, or cases of leukaemia or lymphoma that have crept across the placenta. And its worth noting that, unlike many other cancer types, both these cancers spring from intrinsically mobile cells (melanocytes and white blood cells, respectively).  But this is the first time that researchers have uncovered the detailed molecular evidence to prove that it is definitely the same cancer in both patients.

In their paper, the scientists suggest that this case tells us that the transfer of cancer cells from mother to developing baby may be more common than previously thought. But the reason that such cases are so rare is thanks to the vigilance of the baby’s immune system. And it could also help to shed light on why tumours evade immune attack in other types of cancer.

Kat


References:
Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0904658106

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