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Mutations in cancerous tumours come and go

A research group from Aarhus reveals how cancer cells change character as a cancer tumour develops and why some cancerous tumours develop very aggressively

Researchers at Aarhus University Hospital and Aarhus University have used the newest gene sequencing technology to study tumours from cancer of the bladder. This has provided a completely new and sensational insight into the changes that take place during the development of a cancer tumour in the urinary bladder.

The research group from the department of molecular medicine has shown that special mutations in a bladder cancer tumour lead to a very aggressive form of bladder cancer.

One of the reasons is a specific enzyme (APOBEC) which gives rise to mutations in one-third of the patients, who thereby demonstrate a very characteristic mutation pattern in their cancerous tumours. The mutations impact a number of genes that help control the structure of the DNA chains. Because of this, the research group are able to show that patients with specific mutations in their cancerous tumour will develop the very aggressive form of bladder cancer.

By repeating the gene sequencing 300 times in the individual tumour, the researchers have obtained in-depth insight into how a tumour is built up of several so-called cell populations, that is cells with a range of common characteristics and properties.

- “We have thus been able to show that some cell populations will disappear when cancer develops, while others increase and will come to dominate the cancerous tumour with a completely new set of mutations," says Torben Ørntoft, who is senior consultant at the Department of Molecular Medicine at Aarhus University Hospital, and professor at Aarhus University.

There is thus a very dynamic development in the cells of a cancer tumour, leading to some patients being susceptible to chemotherapy, while others are not.

The research group’s results will be published in the prestigious journal Cell Reports and will contribute to providing a new and much more in-depth insight into the cell populations that constitute a bladder cancer tumour.

 

Facts

  • Gene sequencing technology means researchers can analyse many more genes than previously by simply using a single blood sample.
  • Department of Molecular Medicine, Aarhus University Hospital: www.moma.auh.dk
  • The Cell Reports journal: www.cell.com/cell-reports

Further information:

Professor, Senior Consultant Torben Ørntoft, tel. +45 7845 5300, mobile +45 2819 2680, email: orntoft@ki.au.dk

Professor Lars Dyrskjøt Andersen, tel. +45 4227 1973