Order of genetic faults may dictate how cancers behave
The order in which certain errors appear in a cell’s DNA may ultimately determine how different cancers behave.
“The methods used in this pioneering research could help improve our understanding of how cancer cells develop mutations and when they do so.” - Dr Áine McCarthy, Cancer Research UK
That is according to a study looking at a group of rare bone marrow disorders called myeloproliferative neoplasms (MPNs).
While the discovery will not have an impact on patient care just yet, it could lead to more personalised treatments further down the line by providing a greater insight into how cancers evolve.
It is the first time that the order in which these faults occur in MPNs has been shown to have an impact on disease severity and response to therapy.
The vast majority of these genetic errors – known as mutations – tend to result from environmental damage, such as smoking and UV exposure, or from spontaneous errors as cells divide.
Dr Áine McCarthy, science information officer at Cancer Research UK – who part-funded the study – said: “The methods used in this pioneering research could help improve our understanding of how cancer cells develop mutations and when they do so.”
The researchers, from the University of Cambridge, examined genetically distinct single stem cells taken from patients with MPNs.
The conditions cause an increased number of blood cells, resulting in a greater risk of blood clots and leukaemia, but they can often be identified earlier than most cancers.
Around one in 10 people with MPNs carry mutations in both the JAK2 gene and the TET2 gene. In the latest study, published in the New England Journal of Medicine, the team was able to determine which mutation came first and study the effect of mutation order on the behaviour of single blood stem cells.
Those who acquire mutations in JAK2 prior to those in TET2 were found to display unusual blood counts over a decade earlier. They were also more likely to develop a more severe red blood cell disease subtype and suffer a blood clot, plus their cells responded differently to drugs that inhibit JAK2.
Study leader, Professor Tony Green, believes the finding will lead to powerful insights into the origins of cancer.
“These results show how study of the MPNs provides unparalleled access to the earliest stages of tumour development,” he said.
Dr Matt Kaiser, Head of Research at Leukaemia & Lymphoma Research – who also funded the study – said: “The technology to do this sort of study has been available only recently and it shows once again how pioneering research into blood cancers can reveal fundamental insights into cancer in general."
Cancer Research UK’s Dr McCarthy echoed the promise of this early stage study, citing the potential impact the findings could have.
“This interesting study suggests that the order in which genetic faults appear can affect how patients respond to different drugs - this insight could help doctors personalise treatment to make it more effective for each patient,” she said.
- Ortmann C.A., Kent D.G., Nangalia J., Silber Y., Wedge D.C., Grinfeld J., Baxter E.J., Massie C.E., Papaemmanuil E., Menon S. & Godfrey A.L. Effect of Mutation Order on Myeloproliferative Neoplasms., The New England journal of Medicine, DOI: 10.1056/NEJMoa1412098
- Image by Erik Schepers from Flickr, CC BY-NC-SA 2.0