An intriguing process for moderating genetic activity responsible for determining how flowers are shaped could form the basis for tests and personalised treatments for a type of blood cancer.
A team of scientists led by The Institute of Cancer Research, London, found that analysing chemical changes in four key genes could provide a valuable tool for doctors assessing prognosis and designing personalised treatments for myeloma.
Myeloma biology usually focuses on DNA changes, but more recently, researchers have begun to appreciate the importance of epigenetic changes – heritable changes in gene activity that are not due to changes in DNA sequence.
Many epigenetic processes, including those controlling how flowers are shaped and the coat colour of mice, involve chemical changes to DNA or the proteins near DNA. One such change is an addition of a methyl group to the DNA (methylation), which can cause genes to be switched off.
Researchers analysed genome-wide DNA methylation data together with gene expression data in patients with myeloma from the MRC Myeloma IX trial.
The study, funded by Myeloma UK, found 195 genes that had changes in methylation that were significantly associated with patient outcome. Increased methylation of four genes – GPX3, RBP1, SPARC and TGFBI – was associated with significantly shorter overall survival. These genes normally have a role in suppressing the growth of tumours, through control of important functions including how a tumour responds to chemotherapy and how tumour cells react to their local environment.
Professor Gareth Morgan, Professor of Haematology at The Institute of Cancer Research (ICR) and Head of the Myeloma Unit at The Royal Marsden NHS Foundation Trust, said: “We are extremely pleased with our findings, which offer the potential of using methylation changes to help select personalised myeloma chemotherapy.
“Patient outcome in myeloma is highly variable and a better understanding of the factors that influence disease biology is essential to understand and predict behaviour in individual patients. Myeloma affects around 4,000 people each year. The average survival time after diagnosis is just three to five years, so new treatment options are urgently needed.”