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Follow the Mutations

07/29/2014
Kayt Sukel

Every time a cell divides, there’s a chance that the resulting cells will take on new somatic mutations. Can these mutations be tracked to determine the lineage of every cell in the body? Find out...


Biology students learn that the cells within an organism all carry the same genome and that phenotypes are due to variation in gene expression. This is not entirely true. Somatic mutations frequently occur after fertilization and get passed on with each round of mitosis, leaving a trail of base pair changes that varies from cell to cell.

Embryonic phylogenetic tree (1)

 

To explore the implications of these mutations, Sam Behjati, a researcher at the Wellcome Trust Sanger Institute Cancer Genome Project, and his colleagues turned to next generation sequencing to examine the number and type of somatic mutations in mouse cells.

“Each cell has a set of mutations that is unique to that cell. That tells you quite a bit about that cell. And, based on its unique and shared mutations, you can see how many times it has divided and how related it is to other cells. So looking at these mutations acts as a bit of a lineage tracer,” said Behjati.

The resulting data allowed the research team to reconstruct an animal’s cellular development from embryo to adult using the mutation patterns. “This can be a fundamental biological tool for people who want to study human development and just understand where different cells come from,” Behjati said.

But this technique should also lead to a better understanding of how cancer develops by shedding light on the relationships between tumor and normal cells.

“There are a lot of cancers that are quite obscure. They’re not like lung cancer, which clearly comes from the lung, or skin cancer that comes from the skin. It’s not entirely clear where some tumors come from,” he said. “But many of those cancers may be formed in utero. And if we follow some of these mutations back, we may be able to see where they come from and that will let us know what we’re really dealing with.”

While this study was done in mouse cells, Behjati believes scientists should be able to create similar developmental lineage trees in humans, as long as the mutation rate in a human cells is similar to that seen in mice.

“We now have a tool that allows us to study an adult animal and study its cellular origins without having anything to do with the embryo. It’s a powerful way of defining what happens to cells without actually having to fiddle around with them. And the hope is that, as we begin to understand how mutations work in normal cells, we can better understand the abnormality we see in cancer cells, too,” he said.

Reference

Behjati S, Huch M, van Boxtel R, Karthaus W, Wedge DC, Tamuri AU, Martincorena I, Petljak M, Alexandrov LB, Gundem G, Tarpey PS, Roerink S, Blokker J, Maddison M, Mudie L, Robinson B, Nik-Zainal S, Campbell P, Goldman N, van de Wetering M, Cuppen E, Clevers H, Stratton MR. Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature. 2014 Jun 29.