The European Research Council (ERC) has awarded its Consolidator Grants. This year's recipients include cancer researcher and geneticist Kim De Keersmaecker (KU Leuven). She will receive two million euros to study so-called 'synonymous mutations' and their potential role in the development of cancer.
The human genome consists of 20,000 genes, which our body 'transcribes' into mRNA. These mRNA molecules, in turn, are translated into the amino acids that enable our cells to carry out their specific functions. That process can go awry when a gene mutates and, in some cases, this leads to the development of cancer cells.
The search for genetic mutations that can cause cancer has long been on the scientific agenda. Thousands of genomes of tumour cells have already been sequenced. But one type of mutations is hardly ever taken into account: synonymous mutations.
Under the radar
Unlike 'regular', non-synonymous genetic mutations, synonymous mutations don't change the amino acids of the proteins they code for, explains Professor De Keersmaecker. "This makes it seem as if they have no effect whatsoever, and they have long been considered to be 'silent' mutations that couldn't possibly play a role in the development of cancer. That is why, in the past couple of years, cancer researchers have mainly focused on other mutations."
"But today, we know that some synonymous mutations can promote the development of cancer through a mechanism that we don't quite understand yet. In the next couple of years, my team and I will, therefore, examine their role."
Looking for synonymous mutations
To detect dangerous synonymous mutations, Professor De Keersmaecker intends to use existing genome databases of tumour cells. "We will focus on datasets of blood cancers such as leukaemia, but also on datasets of tumours such as skin, breast, and brain cancer. In total, we will analyse approximately 11,400 samples by means of algorithms that can detect synonymous mutations. That has never been done before: because synonymous mutations have always seemed completely irrelevant."
In the second phase of the study, the team will examine which synonymous mutations - picked up by the algorithms - can transform cells into cancer cells. "We will test approximately fifty mutations in our lab to find out which of these synonymous mutations may not be as innocent as they seem. We also want to study the mechanisms through which these mutations promote cancer. This may offer new insights that can also improve our understanding of non-synonymous mutations."
Open science
Professor De Keersmaecker intends to make all her results publicly available. "When we have completed our analysis, we want to present all our results on a website. This will allow other researchers to look up the name of a gene and find out which synonymous mutations have already been discovered for that gene. We also want to develop a software package for bioinformaticians, so that they can use our methods on other datasets."
"By sharing our data, we're hoping to raise awareness: we must not underestimate the importance of synonymous mutations, and there's still a lot of work to be done."
