Scientists at the Babraham Institute in Cambridge have found a way to detect large-scale changes to the structure of the genome in cancer cells, which could enhance cancer diagnosis and the use of targeted treatments.
Their report outlines a new application of a technique called Hi-C, which allows scientists to map how genetic material is arranged inside cells.
By analysing this information, researchers can reliably identify major genetic changes that other methods may miss. This all comes at a lower cost than standard DNA sequencing methods.
First author on the paper, Dr Louise Harewood, said: “Chromosomal rearrangements are seen both in the general population and in the majority of cancers. Detection of chromosome rearrangements in patients can be troublesome and many can be missed. This can be detrimental, particularly in oncology where rearrangements can play both diagnostic and prognostic roles.”
The scientists, led by Professor Peter Fraser, used Hi-C to examine the genome of cancer cells from six people with brain tumours. They were able to identify major genome changes, often with pinpoint accuracy.
Their approach allows doctors and scientists to study genetic changes in the wider context of the whole genome and Hi-C could become a powerful tool for understanding the complex genetic changes found in many cancers.
Professor Fraser, said: “Hi-C could play a pivotal role in the detection of chromosomal abnormalities and may aid the discovery of new fusion genes. The technique works with much lower quality samples than current techniques and has the additional advantage of being able to provide copy number information from the same data. This all comes at a significantly lower cost than standard methods that use DNA sequencing.”
Moving genes about could help cells to respond to change according to scientists engaged in separate research at the Babraham Institute and the Weizmann Institute, Israel.
Their study reveals that each gene doesn’t have an ideal location in the cell nucleus. Instead, genes are always on the move.
Researchers examined the organisation of genes in stem cells from mice. They showed that the cells continually remix their genes, changing their positions as they progress through different stages.
The work suggests that moving genes about in this way could help cells to fine-tune the volume of each gene to suit the cell’s needs.
Co-first authors, Dr Takashi Nagano in the UK and Yaniv Lubling in Israel have collected and individually analysed information from more than 4,000 cells.
Dr Nagano said: “We’ve never had access to this level of information about how genes are organised before. Being able to compare between thousands of individual cells is an extremely powerful tool and adds an important dimension to our understanding of how cells position their genes.”
Lead author from the Babraham Institute, Professor Peter Fraser said: “We typically see that changes to gene activity have a great impact on health, disease and evolution. It’s now obvious that genome organisation may have a part to play in this and our research shows that the effects of location on genes may be a constantly moving target. Understanding how the genome is controlled during this constant re-shuffling is an important step towards understanding how our genomes and genes effect our lives.”
The team now plan to carry out further research.