Researchers from the Wellcome Sanger Institute, the University of Cambridge and collaborators have uncovered the interplay between cancer-driving genetic mutations and inherited genetic variants in a rare form of blood cancer.
The study reveals how inherited genetic variants can cause mutations in a particular gene and whether they increase the risk of developing myeloproliferative neoplasms (MPNs).
Responsible for around 4,000 cases in the UK every year, MPNs are a group of rare, chronic blood cancers where bone marrow overproduces blood cells, resulting in blood clots and bleeding.
In some cases, MPNs can also progress into other forms of blood cancer, including leukaemia.
When performing routine blood tests, researchers record known information about these genes to further analyse the variation and provide a genetic risk score to determine how likely an individual is to develop a disease.
Researchers combined multiple comprehensive data sets on the known somatic driver mutations that occur in MPN, inherited genetic variants and genetic risk scores from individuals with MPN.
The large-scale study, published in Nature Genetics, found that inherited variants that cause natural blood cell variation in the population also impacted whether a JAK2 somatic mutation could cause MPN.
JAK2 genes provide instructions for making a protein to promote the growth and division of cells. These gene types have previously been linked to random somatic mutations in MPN.
Furthermore, researchers also revealed that individuals with an inherited risk of having a higher blood cell count could display MPN features in the absence of cancer-driving mutations.
Professor Nicole Soranzo, co-senior author, Wellcome Sanger Institute and the University of Cambridge and Human Technopole, Italy, said: “Common variants in these genes also affect blood cancers, independent of causative somatic mutations…, [which] confirms a new important contribution of normal variability beyond complex disease [and contributes] to our understanding of MPNs and blood cancer more generally.”
Despite having an impact on the current clinical predictions of disease development, additional research is required to understand the biological mechanisms behind how inherited genetic variants can influence the chances of developing rare blood cancer.
Further knowledge could accelerate drug development and interventions to reduce the risk of disease.
