Posted: August 2, 2012
Analyses of TCGA Whole Genome Sequencing Data Elucidate the Role of Transposable Elements in Tumorigenesis
Pritty Patel Joshi
Using whole genome sequencing data from The Cancer Genome Atlas (TCGA), a team of researchers at Harvard Medical School have identified transposable elements as a probable source of novel mutations in multiple tumor types. Their work, published June 2012 in Science, could offer novel strategies for the development of targeted therapeutics against multiple cancers.
Transposable elements or ‘jumping genes’ are mobile regions of DNA that, for unclear reasons, often travel to new sites in the genome or paste a copy of themselves into multiple genomic locations. Scientists know that transposable elements exhibit strong mutagenic potential, yet the role of these genetic elements in tumor formation has not been thoroughly examined. Now, Peter J. Park, Ph.D. and his colleagues offer insights into the specific contributions of transposable elements to different cancers.
Transposable Elements Have the Capacity to Introduce ‘Driver’ Mutations in Some Cancer Cells
The team of researchers developed a computational method, Tea (transposable elements analyzer), to determine the exact position and insertion method of transposable elements in cancer genomes. They applied Tea to whole genome sequencing data from colorectal, prostate, ovarian, multiple myeloma, and glioblastoma cancers and their matched normal tissue. These analyses identified almost 200 transposable element insertions, a subset of which occurred in 62 genes including known tumor suppressors.
The scientists found that transposable element insertions occurred in genes that are frequently mutated in cancer. These insertions often altered the expression of the affected genes. Based on these findings, the authors propose that transposable element insertions could actively contribute to the development of cancer by introducing mutations that disrupt gene expression.
Interestingly, transposable element insertions were found in the epithelial-derived cancers, including colorectal, prostate, and ovarian, but none occurred in the brain or blood-borne cancers. Of the epithelial cases, colorectal tumors showed the highest number of insertion events with one sample harboring more than 100 insertions. This colorectal tumor displayed unique molecular characteristics, distinguishing it from the other colorectal tumors examined in the study. According to the authors, these differences suggest that the activity of transposable elements could vary by tissue type and could be used to define distinct tumor subtypes.
Targeting Transposable Elements Offers a Novel Area of Cancer Prevention and Treatment Strategies
The researchers in this study used TCGA data in an effort to more clearly define the role of transposable elements in multiple cancers. Their findings suggest that transposable elements can ‘drive’ tumorigenesis by introducing mutations that offer a selective advantage to cancer cells. This work lays the foundation for researchers to determine the full extent to which transposable elements contribute to cancer.
Future analyses of additional TCGA cancer genome sequence data with Tea software could reveal the prevalence of specific types of transposable elements in certain cancers. Furthermore, since many transposable elements share traits with some viruses, research efforts aimed at controlling viruses could similarly be used to suppress mobile elements in tumor cells. Such research aims could offer a largely unexplored avenue for the development of targeted therapies and prevention strategies for multiple cancers.
Lee, E., Iskow, R., Yang, L., Gokcumen, O., Haseley, P., Luquette, L.J. III., Lohr, J.G., Harris, C.C., Ding, L., Wilson, R.K., et al. (2012) Landscape of Somatic Retrotransposition in Human Cancers Science. [published online ahead of print June 28, 2012]. Read the full article.
For more information about Tea, visit the companion site for the Tea repeat analysis pipeline.
