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First study of the genomic architecture of the human placenta

15 March 2021
Appeared in BioNews 1087

The human placenta has a genetic structure resembling that of a tumour and has many of the gene mutations found in childhood cancers, according to scientists.

The study, published in Nature, is the first high-resolution analysis of the genomic architecture of the placenta. It not only confirms that the structure of the placenta is different to that of other organs, but shows that it harbours many cancer-causing genetic defects, supporting the theory that gene mutations are corrected or avoided by the fetus.

'Our study confirms for the first time that the placenta is organised differently to every other human organ, and in fact resembles a patchwork of tumours,' said senior author Professor Steve Charnock-Jones from the University of Cambridge. 'The rates and patterns of genetic mutations were also incredibly high compared to other healthy human tissues.'

Previous research has shown that in one to two percent of pregnancies, placental cells can have a different number of chromosomes to fetal cells. Despite these genetic defects, the placenta usually functions normally. However, problems with the placenta can cause harm to a mother and fetus, such as growth restriction and stillbirths.

To further investigate this, researchers from the Wellcome Sanger Institute in Hinxton, Cambridgeshire, and the University of Cambridge performed whole genome sequencing of 86 bulk samples and 106 tissue microdissections from 42 placentas. They found that each biopsy was a genetically distinct cell population derived from a single common ancestor, indicating a link between the formation of the placenta and cancer development.

For example, in one biopsy, three copies of chromosome ten were found in each cell (two from the mother and one from the father) instead of the usual single copy from each parent. But other biopsies from the same placenta and the fetus carried two copies of chromosome ten, both from the mother. Further analysis also revealed specific patterns of mutations commonly found in childhood cancers, such as neuroblastoma, with more of these mutations in the placenta than in the cancers themselves.

'The placenta is akin to the 'Wild West' of the human genome, completely different in its structure from any other healthy human tissue,' said senior author Dr Sam Behjati, from the Wellcome Sanger Institute. 'It helps to protect us from flaws in our genetic code, but equally there remains a high burden of disease associated with the placenta.'

Future studies using larger sample sizes could now help uncover the causes of complications and diseases that occur during pregnancy. 'Our findings provide a rationale for studying the association between genetic aberrations in the placenta and birth outcomes at the high resolution we deployed and at massive scale,' Dr Behjati added.

SOURCES & REFERENCES
Human placenta found to 'resemble a patchwork of tumours'
Science Focus |  11 March 2021
Inherent mosaicism and extensive mutation of human placentas
Nature |  10 March 2021
Placenta is a dumping ground for genetic defects
Wellcome Sanger Institute |  10 March 2021
Placenta resembles a tumour and is dumping ground for genetic defects, say scientists
The Independent |  10 March 2021
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