Posted: July 12, 2011
TCGA GBM Data Analysis Reveals a MicroRNA that May Affect GBM Tumor Development and Patient Survival
One of The Cancer Genome Atlas’s (TCGA) major strengths is the multidimensional nature of its genomic data. Instead of annotating just one type of alteration, TCGA collects data on all the major types of cancerous genetic changes. Since its completed characterization of the glioblastoma multiforme (GBM) genome, an increasing number of studies are emerging using the publicly available data. GBM is one of the deadliest adult cancers, with median survival of little more than a year. A study published in the January 2010 issue of Proceedings of the National Academy of Sciences (PNAS) demonstrated the value scientists can glean from TCGA’s comprehensive cache of data. The Harvard researchers used TCGA GBM data on copy number, microRNA expression and gene expression to illuminate a new role for a microRNA in GBM development and patient survival.
Scientists are increasingly interested in the involvement of microRNAs in tumor development. MicroRNAs are short sequences of nucleotides that code for small RNA molecules. These tiny RNA molecules can turn genes on or off, leading to cancerous changes.
miR-26a is a MicroRNA that is Amplified in Many GBM Tumors
Analyzing TCGA’s copy number and microRNA expression data in GBM, the researchers found that the sequence for a microRNA called miR-26a is amplified in many tumors. Frequently in GBM tumors and other cancers, there are several more copies than usual of a segment of chromosome 12. This phenomenon is called chromosomal amplification. miR-26a is located in the amplified part of chromosome 12 in many of the GBM tumors. This amplification probably leads miR-26a to be overexpressed in some tumors. This information led the authors to suspect that miR-26a is overactive in some GBM tumors, perhaps inhibiting tumor suppressor genes and thus promoting GBM growth.
Further statistical analysis of the TCGA data revealed that miR-26a likely inhibits, or targets, three tumor suppressor genes called PTEN, RB1 and MAP3K2/MEKK2. These genes are frequently mutated in many other cancers. The researchers guessed that miR-26a aids GBM development by turning off these tumor suppressors.
miR-26a Contributes to GBM Development by Turning off Tumor Suppressors
Cell culture experiments supported this theory. When the scientists overexpressed miR-26a in GBM cell cultures, expression of the tumor suppressors PTEN, RB1 and MAP3K2/MEKK2 decreased. Cells with overexpressed miR-26a showed more cancer-like growth. When they transplanted GBM cells containing overexpressed miR-26a into mice, the resulting tumors were larger than those from GBM cells lacking overexpressed miR-26a. TCGA data also indicated that patients with increased miR-26a expression in their tumors had shorter survival times.
As a whole, the scientists say, miR-26a is overexpressed in some patients’ GBM tumors, enhancing GBM development and leading to shorter survival times. The group was able to show that miR-26a’s tumor promoting properties result from its ability to turn off important tumor suppressors. miR-26a may represent a potential new target for drug treatments.
As more of the cancer genomics community uses TCGA’s data, a clearer picture of these complex diseases will emerge. The current study illustrates how scientists can use TCGA’s multidimensional data to tackle the genetic intricacies of GBM and other cancers.
Kim, H., Huang, W., Jiang, X., Pennicooke, B., Park, P.J. and Johnson, M.D. (2010) Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship. Proc Natl Acad Sci USA. (5):2183-2188. Read the full article.