{"id":26940,"date":"2021-04-06T10:02:30","date_gmt":"2021-04-06T10:02:30","guid":{"rendered":"https:\/\/scienceblog.cancerresearchuk.org\/?p=18418"},"modified":"2024-11-03T15:14:59","modified_gmt":"2024-11-03T15:14:59","slug":"an-unexpected-find-clues-about-the-genetics-of-childrens-cancer-found-in-the-placenta","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/an-unexpected-find-clues-about-the-genetics-of-childrens-cancer-found-in-the-placenta\/","title":{"rendered":"An unexpected find: clues about the genetics of children\u2019s cancer found in the placenta"},"content":{"rendered":"
A cartoon graphic of a foetus, showing womb anatomy.<\/p>

” data-medium-file=”https:\/\/scienceblog.cancerresearchuk.org\/wp-content\/uploads\/2021\/04\/Placenta_hero-300×168.jpg” data-large-file=”https:\/\/scienceblog.cancerresearchuk.org\/wp-content\/uploads\/2021\/04\/Placenta_hero.jpg”><\/p><\/div>

It has long been understood that the placenta is a very different organ to the rest of the body.<\/p>

But no-one knew quite how different. Last month, a fascinating piece of research shed light on the unique genetic structure of the placenta, revealing a level of detail that\u2019s never before been seen.<\/p>

Researchers based at the<\/span><\/span> Wellcome<\/span><\/span> Sanger Institute and the University of Cambridge have produced the first high resolution map of the genetic architecture of the placenta, publishing their findings in<\/span><\/span> Nature<\/span><\/span><\/a><\/em>.<\/span><\/span> To their surprise, the team discovered that the genetic structure of the placenta<\/span><\/span> contains similar<\/span><\/span> DNA faults (mutations)<\/span><\/span> to those<\/span><\/span> frequently seen in<\/span><\/span> children\u2019s<\/span><\/span> cancers.<\/span><\/span><\/p>\n

But the placenta still functions entirely as it should.<\/p>\n

\n

\u201cWhat we found completely blew our socks off.\u201d \u2013 Dr Sam Behjati<\/em><\/strong><\/p>\n<\/div>\n

Dr Sam<\/span> Behjati<\/span> is one of the lead researchers involved in the project.<\/span> Behjati<\/span> is a paediatrician scientist who has recently been funded as part of the<\/span><\/span> Cancer Research UK\u2013Children with Cancer UK Innovation Awards<\/span><\/span><\/a>. He spoke to us about what the latest results could mean for the future of children and young people\u2019s cancer research.<\/span><\/span><\/p>\n

Retracing steps to the first cell division<\/h2>\n

In the earliest days of pregnancy, a fertilized egg will embed itself into the wall of the uterus and begin dividing from one cell into many. Cells will begin to specialise into various cell types \u2013 a process known as differentiation \u2013 to create the foetus, with some splitting off to form the placenta.<\/p>\n

\u201cMagdelena Zernicka-Goetz, an eminent embryologist, first put out this idea in 2005 that when the egg divides, one cell makes most of the embryo and the other cell makes most as a placenta,\u201d explains Behjati. \u201cAnd so we were interested in that very first cell division, and whether it\u2019s got something to do with the ability of the fertilised egg to get rid of genetically abnormal cells.\u201d<\/p>\n

The team at the Wellcome Sanger Institute retraced the evolution of cells back to the very first cell divisions of the fertilised egg. They read the entire DNA sequence, using a technique called whole genome sequencing, of cells from 42 different placentas, with samples taken from distinct areas of each placenta.<\/p>\n

What they found was something that has never been seen before.<\/p>\n

The \u2018wild west\u2019 of the human genome<\/h2>\n

\u201cWhat we found completely blew our socks off,\u201d says Behjati.<\/p>\n

\u201cWe sequenced a pea sized chunk of placenta, and found it has the genetic structure similar to a tumour. And then we took another chunk from a different area of the placenta, and it\u2019s structured like another, independent tumour.\u201d<\/p>\n

What the team discovered is that if a cell has a mutation, for example, an abnormal number of chromosomes, it gets pushed to the outside of the embryo, and ends up in the placenta. \u201cThe placenta is kind of the \u2018wild west\u2019 of the human genome, it genuinely does not seem to care how riddled with mutations it is,\u201d says Behjati.<\/p>\n

The team also found that, when you looked at the DNA of cells in different parts of the placenta, they all looked different, forming distinct clusters of cells. This process is very similar to the formation of a cancer, which often begins with changes in a single cell.<\/p>\n

The next step was for the team to analyse the mutations in more detail.<\/p>\n

In a number of the biopsies, they came across a few very specific mutations that are known to be the drivers of a number of children\u2019s cancers.<\/p>\n

\u201cThe mutation signature that we saw<\/span><\/span> in the placenta cells<\/span><\/span> is one of childhood cancer, specifically of<\/span><\/span> neuroblastoma<\/span><\/span><\/a> and<\/span><\/span> rhabdomyosarcoma<\/span><\/span><\/a>, which has never been seen in normal tissue before. It was completely unexpected,\u201d explains<\/span><\/span> Behjati<\/span><\/span>.<\/span><\/span><\/p>\n

Back to cancer<\/span><\/h2>\n

The results of th<\/span>e<\/span> study have<\/span> wide-ranging implications, as the Sanger Institute explains<\/a>.<\/span> But what does all this mean for the future of<\/span> children<\/span>\u2019s<\/span> cancer research?<\/span><\/p>\n

\u201cThe<\/span> reason<\/span> I<\/span> study mutations in normal tissue is because<\/span> mutations<\/span> are<\/span> the<\/span> cause<\/span> of<\/span> cancer<\/span>.<\/span> T<\/span>herefore, we need to understand a lot about mutations<\/span> in order to<\/span> understand cance<\/span>r<\/span>,<\/span>\u201d<\/span> explains<\/span> Behjati<\/span>.<\/span><\/p>\n

He<\/span> adds<\/span> that it<\/span> was<\/span> surprising th<\/span>at you<\/span> can get<\/span> an organ<\/span> that<\/span> contains many<\/span> cancer mutations, but that functions entirely as<\/span> it<\/span>\u2019<\/span>s supposed to.<\/span><\/p>\n

\u201c<\/span>R<\/span>eally what we need to get down to is that<\/span> a<\/span> childhood cancer and<\/span> a<\/span> human placental tissue have got the same genetic defects, yet one is a cancer and the other is not.<\/span><\/p>\n

\u201cWe are getting closer and closer to pinning down what the difference is. Initially we thought the difference<\/span> was<\/span> just the mutations. But it is now clear the difference isn\u2019t just the mutations, it\u2019s something else<\/span>,<\/span> plus the mutations.\u201d<\/span><\/p>\n

Professor<\/span><\/span> Christine Harrison is<\/span><\/span> part of another team who has recently received an<\/span><\/span> Innovation Award<\/span><\/span><\/span><\/a>, looking into the<\/span><\/span> role of aneuploidy to treat<\/span><\/span> children\u2019s<\/span><\/span> cancers<\/span><\/span><\/span><\/a> in the development of childhood cancers and how it may be exploited to improve treatment.<\/span><\/span><\/p>\n

Aneuploidy is when a cell has one or more extra or missing chromosomes. Aneuploidies are often found in the cancer cells of children and young people with different types of cancer, and was also seen in the genetic structure of the placenta.<\/span><\/p>\n

\u201cThis fascinating research by Dr Behjati and his team has discovered approximately half of the placental samples studied showed evidence of chromosomal gains and losses (aneuploidies). These findings are unique for non-cancerous human tissue, specifically the changes in aneuploidy,\u201d explains Harrison.<\/span><\/p>\n

Harrison adds that the results from this paper could have implications for the future of chromosome and childhood cancer research.<\/span><\/p>\n

\u201cSome of the genetic changes reported here are prevalent in childhood cancer, in particular the aneuploidies.\u201d She adds that studying the changes seen in the placenta in larger studies may help to provide clues about the development of certain cancers, particularly those that arise in very young children, and provide information towards how these cancers may be prevented.
<\/span><\/p>\n

Lilly<\/em><\/p>\n

More on this topic<\/h3>\n<\/p>\n

Source<\/a><\/p><\/div>","protected":false},"excerpt":{"rendered":"It has long been understood that the placenta is a very different organ to the rest of the body. But no-one knew quite how different. Last month, a fascinating piece of research shed light on the unique genetic structure of the placenta, revealing a level of detail that\u2019s never before been seen. Researchers based at [...]","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-26940","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26940","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=26940"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26940\/revisions"}],"predecessor-version":[{"id":43874,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26940\/revisions\/43874"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=26940"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=26940"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=26940"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}