Researchers Analyze Connection between Extra DNA and Cancer Evolution


Published Date : Apr 26, 2018

Glioblastoma (GBM) is among the aggressive and common forms of brain cancer. The cancer responds poorly to most standard treatments and often has a survival rate of two years that too for only about 15% of those diagnosed. However, research studies have started to give a better understanding regarding the processes that form the basis of cell-to-cell differences within these tumors—an important finding as these differences largely influence resistance to therapy. Researchers are now delving deeper into the understanding regarding the pathways that can be targeted to block the progression of glioma.

Until this point, researchers from the Jackson Laboratory and the Hermelin Brain Tumor Center, Detroit have tracked alterations in genes in patient samples during the evolution of the cancer cell in culture, before and post treatment in patients, and xenograft derived from patients in mouse models. In their recent study papers, the researchers have reported that the progression of the cancer was frequently driven by oncogenes, the cancer-promoting genes, on extrachromosomal pieces of DNA.

Detailed analysis of the cancer cells from patients to culture to mouse subjects have demonstrated that, for large parts, the same genomic lesions were reserved by the cells. This indicated that the mouse subjects can prove to be an effective and relatively accurate platform for experimentations regarding glioma. The primary limitation, however, was that in certain cases, the number of oncogene copies were different between the cultures and tumors and the xenografts derived from them.

When researched why the implication levels of oncogenes differed, the researchers found out that the difference was caused due to the oncogenes that were not a part of gene sequence as seen in general cases. Instead, the difference was seen on separate DNA pieces, called the extrachromosomal (ec) DNA. Further study demonstrated that several cases of oncogene amplification observed in glioma were associated with ecDNA elements.

Researchers believe that targeting ecDNA carries significant potential of developing new treatments for the cancer. Researchers are now working towards the development of sequencing-based procedures for identifying ecDNA more effectively. If the mechanism behind the formation of ecDNA is understood well, ways of blocking the mechanism can be researched upon, gaining new directions about the prevention and even the formation of a number of cancers.