The importance of prognostic biomarkers in improving risk stratification in Wilms’ Tumour

Research led by BRC funded Professor Kathy Pritchard-Jones has demonstrated the importance of prognostic biomarkers in improving risk stratification in Wilms’ Tumour (WT).85% of children diagnosed with WT are classified as having low or intermediate risk tumours. These children have a 90% chance of survival but because they make up the majority of patients, they also have the largest number of relapses. Survival after relapse is less good in WT, with 50% of relapses being fatal. Novel biomarkers may provide data which could improve risk assessment of tumours and maximise the chance of first line therapy being successful (this is measured as event-free survival (EFS)).

Kathy Pritchard-Jones’ group was the first to show that a specific change in the genetic material of the tumour (additional material from chromosome 1, known as 1q gain) is associated with poorer outcomes. She has now led a new international study to analyse genomic copy number changes at several chromosomal regions in nearly 600 WT patients from 7 countries in Europe.

Findings published in The Journal of Clinical Oncology show that 1q gain is one of the most common copy number changes in WT and demonstrate that 1q gain is significantly associated with poorer EFS. Other notable genomic changes associated with poorer EFS, included MYCN gain and TP53, genes that are also abnormal in some other high risk childhood cancers.  However, when all of the other tumour and patient characteristics are taken into account, gain of 1q is not significantly associated with poorer survival, suggesting that further molecular features of the tumours need to be studied before patient treatment can be altered. Prof Pritchard-Jones’ group is now using next generation DNA sequencing approaches to do this.