Newly Discovered DNA Patterns Show the True Process by Which Glucose Metabolism Affects Cancer
A new five-year study exploring the intricate way DNA patterns and glucose metabolism leads to the development and evolution of cancer was set up by Dr. Thomas Graeber, professor of medical and molecular pharmacology at UCLA and member of the Jonsson Comprehensive Cancer Center’s Cancer Nanotechnology Program. Together with his associates, Dr. Nicholas Graham and Dr. Aspram Minasyan, Graeber established a complex, multi-layer study of DNA patterns seeking to shed more light on the way in which the patterns in tumor cells affect tumor evolution in a highly selective and specific manner.
Laying the Groundwork
Compared to less aggressive cancers that have a complete genome, more aggressive tumors have been found to have aberrant DNA patterns that were previously thought to be random. Through reprogrammed cellular metabolism, tumor-forming cells are transformed in numerous ways, and also alter their ability to generate energy from glucose, fueling tumor growth even more.
The findings that Graeber’s team is responsible for tied in the process of glycolysis, the higher levels of glycolytic activity associated with aggressive cancers and the CNA (copy number alteration) patterns that were previously thought to be completely random. It was discovered that these patterns were subsequently found to reflect predictably changing genomic transformation in a number of different cancer types.
While modern science focuses on targeting specific cancer genes for DNA mutations, arguing that special oncogenes and tumor suppressor genes need to be regulated in order for cancer to be kept under control, the latest research suggests there are many recurring CNA patterns that have nothing to do with canonical cancer genes. This is also the premise for Graeber’s research, which seeks to use copy number alteration to profile a wide variety of tumors, linking them through recurring patterns in genes deleted or amplified in DNA.
The Purpose and Findings of the Study
Over a period of five years, Graeber and his team analyzed CNA data from cancer cell lines, as well as both human and mouse tumors, following the progress of 15 different types of cancer. The study revealed that the patterns associated with DNA deletion and amplification showed many predictable implications particularly regarding glycolytic activity and the fast growth of cancerous tumors.
Human tumors and those analyzed through mouse models were compared to study the role of enzymes in the process, and 26 different DNA regions were discovered containing 11 enzymes associated with glycolysis pathways and genes that assist tumorous growths.
Genetic engineering was then used to show that the enzymes can directly alter the CNA signature. Through cell samples taken at different points in time during the tumors’ development, the researchers demonstrated how the CNA patterns could actually form the cancer genome.
This was one of the first studies to ever use genome-wide CNA signatures for the purpose of defining new varieties of tumors and identify oncogene related point mutations. The final results may allow researchers to create improved cancer models in the future and further advance the development of better targeted treatments that could work for each type of cancer.
The sheer amount of data gathered during the study is enough to allow scientists to understand the patterns of genome alterations at an entirely new level. The role of glucose metabolism and its importance in the development of aggressive cancerous tumors is also expected to be better understood through the use of these patterns, ultimately leading to new practical treatments in the near future.