Genes helping to predict the recurrence of kidney cancer

DNA sequencing supporting a greater understanding of the disease and ways to treat patients

By Sean Tarry

DNA sequencing has come a long way over the course of the past 50 years or so. From its earliest breakthroughs with Walter Fiers’ sequencing of the DNA of a complete gene in 1972 to the completion of The Human Genome Project in 2003 and the very latest in targeted DNA sequencing, it’s an area of research and study that’s elevated our understanding of life and the ways to properly preserve it to levels not thought of prior. And, most recently, after a lengthy study into kidney cancer, sequencing has revealed a much more effective way to predict the likelihood of the disease recurring in patients.

Developing a greater understanding
The study, which spanned the better part of a decade, was conducted by a team of 44 researchers representing 23 different institutions across Europe and Canada, successfully links the genetic changes that occur in kidney cancer directly to patient outcomes and results. It’s a breakthrough within the area of kidney cancer research that could pave the way toward even greater understanding of the disease. And, according to the study’s CO-lead investigator Dr Naveen Vasudev, Associate Professor and Honorary Consultant in Medical Oncology in the Leeds Institute of Medical Research at St James’s, it’s an understanding that could also lead to more personalized treatment for patients suffering with the disease.
“Accurately determining the risk of recurrence is very important,” he says. “As well as helping us identify how often patients need to be seen by their doctors, it helps us to decide who to treat with immunotherapy. This treatment has recently been shown to reduce the chances of the cancer coming back but can cause side-effects. The danger currently is that some patients may be over-treated, so being able to better identify patients at low risk of recurrence is important since they could be spared more treatment.”

DNA sequencing critical
The breakthrough was made by leveraging DNA sequencing techniques to study changes in the DNA of more than 900 kidney cancer samples, identifying 4 groups based on the mutations in 12 specific genes within the DNA. In addition, considerations were made based on whether or not patients had experienced a recurrence of the disease before. Results revealed that an overwhelming 91 per cent of patients within one of the mutation groups managed to avoid recurrence five years after their surgery. These patients, the study proffers, may not require as much treatment. Whereas, 51 per cent of patients within another mutation group were found to have remained disease-free during the same amount of time, suggesting that this group requires a more aggressive treatment regimen.

Outdated methods
It’s estimated that more than 400,000 people around the world are diagnosed with kidney cancer each year, including 8,100 diagnoses occurring in Canada. Given the fact that a discouraging 30 per cent of localized kidney cancers recur after post-surgery, combined with outdated methods by which doctors determine the risk of recurrence, which include studying features like the size of the tumour and how aggressive it appears under a microscope, many are suggesting that a more accurate assessment has been required for some time. And, based on findings within the recent study, Yasser Riazalhosseini, Assistant Professor of Human Genetics, and Head of Cancer Genomics at the Victor Phillip Dahdaleh Institute of Genomic Medicine at McGill University, says that this latest breakthrough could be the right solution.
“Our research shows that it may be possible to improve the way we determine risk in each patient by looking at the genetic mutations present in their cancer,” he explains. “Mutation analysis using DNA sequencing is already being used to help patients with other types of cancer and could be readily applied to patients with kidney cancer.”

More personalized treatment
And, adds the study’s CO-lead investigator, Vasudev, the timing of the research team’s findings couldn’t be better, providing a glimpse into the potential to apply them toward creating more personalized care and treatment for patients suffering from kidney cancer.
“Development of new treatments for kidney cancer has lagged behind other cancers and we largely continue to adopt a ‘one size fits all’ approach. Genomics—the study of genes and how they interact with each other—is a key area of development in patient care. Here we show how genomics might be applied to patients with kidney cancer, potentially creating more personalized treatment options for thousands of patients each year.”