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Mutations that cause adult blood cancer occur in childhood

The findings of a new study have revealed that mutations driving blood cancer in adults may have been acquired in early childhood. Detecting these mutations early in life may allow for preventative measures to be taken in individuals at risk of cancer.

Blood cancer mutations

Blood cancer is the fifth most common cancer in the UK and the third biggest cause of cancer death, killing around 15,000 people each year. The risk of blood cancer also increases with age, with 40% of patients diagnosed aged 75 or older. 

Unfortunately, tumours develop quickly in blood cancer patients. This makes it very difficult to diagnose the cancer early. Therefore, there isn’t a chance to apply early treatment, which would provide a higher chance of survival.

Despite the quick development of these cancers, previous studies have found evidence of cancer-driving mutations being present in the blood of healthy individuals. Some of these individuals have then gone on to develop cancer. The team behind a new study, published in Nature, investigated this further to better understand the timelines of cancer evolution. 

Timing of mutation occurrence

The team studied 12 patients with myeloproliferative neoplasm (MPN), a type of blood cancer that causes overproduction of blood cells in the bone marrow. A key causative mutation of MPN is V617F in the gene JAK2, which is present in the majority of patients.

First, the researchers applied whole genome sequencing (WGS) to blood cell clone samples from the patients. The results showed that ten out of the 12 patients carried the JAK2 mutation. Interestingly, all patients had mixtures of colonies with and without driver mutations. This indicated that mutated cells were able to co-exist alongside normal blood production.

Using their WGS data, the team were able to reconstruct phylogenetic trees for each individual patient. These trees allow for the estimation of mutation acquisition. Surprisingly, the results showed that in all patients, both JAK2 and other blood cancer driver mutations occurred in childhood, before 13 years of age. In fact, in one patient the JAK2 mutation occurred before birth, only a few weeks after conception. Despite how early the patients acquired the mutations, they all only showed cancer symptoms much later in life. The mean time between mutation acquisition and cancer diagnosis was 34 years.

Clonal expansion

Next, the researchers used the phylogenetic trees to investigate the multiplication of mutated cells over time. Unsurprisingly, it was found that the slower the mutations proliferated, the later in life cancer symptoms became apparent. In addition, the patients who had the shortest time periods between mutation acquisition and diagnosis had multiple driver mutations, not just a mutated JAK2 gene. Those where JAK2 was the only mutated driver had much slower mutation expansion over time.

Future work

Until now, scientists did not know that mutations driving blood cancer could be acquired so early in life.

It is hoped that, in the future, detection of such mutations could be used to predict cancer risk. Nonetheless, further research will be needed to see if this is possible. If so, therapies could be developed to slow down or prevent the growth of cancer in high-risk individuals.

Senior author Dr Jyoti Nangalia said:

“Our research shows that cancer-driving mutations can occur in early childhood, even in the womb, to result in cancer diagnosis decades later. This is not something we were expecting. Blood cancer impacts thousands of lives every day and research such as ours into the timing and pace of how different cancers develop is crucial if we are going to find new ways to prevent these conditions. The success of our approach for tracking the origin and growth of this blood cancer could be applied to many other cancers and diseases.”

Picture credit: Canva

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Blood / Cancer / Mutations