Discovery of several hundreds of potential cancer genes

To chart the genes that are involved in the development of leukemia – cancer of white blood cells- researchers Jaap Kool, Anthony Uren and colleagues investigated 10.000 mutations in 500 leukemia. Analysis of the 10.000 mutations resulted in the identification of more than 250 new candidate cancer genes.

The researchers used a technique called ‘retroviral insertional mutagenesis’ in mice. This technique is based on the ability of retroviruses to incorporate their DNA into the genome of host cells. The integrated viral DNA can influence the activity of nearby host genes or disrupt the genetic code of a host gene.

If the affected gene is a cancer gene, the viral integration may give rise to the development of a tumor. Host genes that are mutated by the virus can subsequently be identified using DNA analysis.

Kool and Uren, both employed in the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital in the research groups of professor Anton Berns and professor Maarten van Lohuizen, and their colleagues were the first to combine ‘retroviral insertional mutagenesis’ with automate ‘high- throughput’ DNA analysis.

This enabled them to identify a far larger number of mutations than comparable studies published to date. Not only did this amount to the identification of more than 250 new candidate cancer genes, it also resulted in the discovery of combinations of cancer genes that collaborate in the development of leukemia.