It is advantageous to know what specific DNA mutations have led to the development of cancer, as this informs treatment decisions. Certain treatments will be much more effective at treating different causes of cancer. It is becoming increasingly common for cancer patients to undergo tests to find these mutations prior to commencing treatment.
A study conducted by researchers at the University of California Santa Cruz Genomics Institute suggests that gene expression analysis could be far more useful than DNA mutation analysis in pediatric patients. In adults, cancers are most commonly caused by DNA mutations whereas in pediatric patients, cancer tends to result from genetic errors during development that alter how genes are expressed. The study has shown the value of conducting gene expression analyses of tumor cells to identify potential targets for therapy.
Gene expression is the process of converting genetic information in the DNA into proteins, which occurs through two key processes. The first stage is conversion of the DNA gene into messenger RNA (mRNA) in a process called transcription. The second stage is translation, where the mRNA directs protein synthesis.
For the study, the researchers analyzed 144 samples of tumors from 128 pediatric cancer patients that were taking part in four separate precision medicine trials in the USA and Canada.
The researchers used the UCSC Treehouse Childhood Cancer Initiative framework for comparative RNA analysis to study gene expression in pediatric cancer patients using RNA sequencing data. The RNA sequencing data from tumor cells shows which genes are active and the level of activity. The more mRNA molecules that are found, the more active the gene.
The researchers compared the RNA sequencing data from the patients with large public genomic datasets to identify unusual expression patterns. Any abnormal gene expression could potentially be driving the growth of tumors. Genes that were being over-expressed and/or their pathways could then potentially be targeted with drugs or other therapies. The researchers also looked at DNA analysis data and compared the two.
The researchers found that in 68% of the tumor samples, RNA sequence analysis was potentially useful for identifying druggable genes and pathways compared to 46% of tumors samples that had undergone DNA mutation analysis. 36% of the samples analyzed by the researchers had druggable over-expressed genes which were not identified by the DNA mutation analysis.
The study was conducted to demonstrate whether it was possible to obtain the necessary data, analyze it, and process it in a short enough time frame for this to be useful for guiding treatment decisions. “We showed for the first time that this framework can be used consistently across separate precision medicine clinical trials,” said, Olena Vaske, Colligan Presidential Chair in Pediatric Genomics at UC Santa Cruz and first author of the study.
Gene expression analysis could provide important clinical and biological information that could be used to determine the best treatments for individual patients. The study also shows how important it is for there to be open sharing and combined analysis of tumor RNA sequencing data from pediatric and young adult patients.
“For the comparative analyses, it’s a numbers game, so the larger the compendium, the more robust the analysis will be. That’s why we believe so strongly in open sharing of data,” said Vaske.
Further information on the study can be found in the paper – Comparative Tumor RNA Sequencing Analysis for Difficult-to-Treat Pediatric and Young Adult Patients With Cancer– which was recently published in Jama Network Open. DOI: 10.1001/jamanetworkopen.2019.13968