The researchers studied the genes in tumours from 4,086 patients and found 592 significant DNA amplifications in 438 cancer patients, suggesting that 5-10% of cancer patients might be suitable for treatment with an existing targeted therapy. In addition to brain and breast cancers, they found significant amplifications in cancer of the colon (5.8%), lung (5.8%), ovary (4%) and pancreas (3%). They were rare or non-existent in liver cancer, leukaemia and myeloma. As might be expected, amplifications of the HER2 gene were found in breast cancer (13.7% frequency), at which the drug trastuzumab is targeted, but it was also found in small subsets of colorectal (1.3%) and lung (0.9%) cancer patients. There were examples of other gene amplifications occurring in cancers other than those for which targeted therapies had been tested and approved.

The researchers also checked whether the amplifications were ones that were responsible for driving the growth of the various cancers. "We cannot be sure that in each case the DNA amplifications we studied were 'drivers' of cancer, but we can look for clues that the genes are likely to be the drivers," explained Dr Rhodes. "If the amplifications involved small, focal regions of the genome that included only the target or only a few genes, then it is more likely that the target gene was a 'driver'. Also, if the target gene was more frequently amplified and amplified at higher levels than neighbour genes, then again it is more likely that the target gene is the 'driver'. Thus, we examined the regions of amplification around the target genes and the most commonly amplified genes in the region and in almost all cases, our target gene under study was the most commonly and most highly amplified gene in the region."

Dr Rhodes concluded: "We envision our work motivating a DNA amplification-guided clinical trial that would test advanced cancer patients for DNA amplification of all relevant targets and then partition patients into treatment arms based on their particular amplification. Such an effort would be costly and could require hundreds of patients; however, our study provides the basis and the frequencies of amplifications that could be expected. We hope that this work will motivate clinicians to consider such an approach."

Source: Compendia Bioscience