Identifying Abnormally Activated Genes To Predict Cancer Virulence
The researchers, from the Institut Albert Bonniot de Grenoble, CNRS, Inserm and Université Joseph Fourier, all in France, worked together with doctors and anatomopathologists from the CHU de Grenoble. They demonstrated that all aberrant activation of several genes specific to other tissues occur in all cancers. For examples, in lung cancer, tumor cells express genes specific to the production of male sperm - these genes should be silent.
Early stages of lung cancer can already be identified by focusing on gene expression in nasal cells, researchers from Boston University Medical Center reported at ATS 2011 International Conference (May 2011).
The authors believe that it may be possible to determine a cancer's virulence with greater accuracy if the genes that are abnormally activated are identified. They add that their findings will help doctors provide patients with more accurate diagnoses as well as more personalized care.
All the cells in a person's body have the same genes. However, not all of them are activated - this depends on the cell's specialization. Some genes are activated while others are repressed. In cancerous cells, the activating and silencing mechanisms of the genes is damaged. Researchers explain that in all cancers there is a kind of "identity crisis" in cancerous cells. In the organs or tissues where a tumor develops, the wrong genes may be activated, genes which are specific to other tissues or to other stages of the development of the organism.
Before this study, scientists had only partially studied this aspect of gene expression.
By concentrating on the genes that are "woken up", the scientists have been able to demonstrated that in the vast majority of cancers, dozens of specific genes in the germline and the placenta are wrongly activated. "This represents a very interesting source of potential biomarkers for characterizing tumors."
Sophie Rousseaux and team looked at the tumors of nearly 300 people at the CHU (Centre Hospitalier Universitaire) de Grenoble. Doctors gathered and analyzed documented patient records over a ten year period, and conserved and annotated tumors after surgical resection. Scientists analyzed the expression of all human genes from these tumors.
They found 26 wrongly activated genes in lung cancer tumor cells which were linked to very aggressive cancers. When these genes are expressed, the cancer tends to be very virulent. The scientists were therefore able to predict which cancers are more likely to recur or cause death, even at the diagnosis stage and even when the tumor is adequately treated.
The team say their study provides a "proof of principle for a new approach in the study and treatment of cancer: the aberrant expression in a tissue or organ of genes specific to other tissues could become a new tool for establishing a prognosis and personalizing therapeutic care."
The scientists still need to explain the link between the mistaken gene expression and cancer virulence. Their approach to lung cancer testing could be used for virtually all kinds of cancer, they added.
The study was sponsored by the the Institut National du Cancer, the Ligue Nationale Contre le Cancer and the Fondation ARC pour la Recherche sur le Cancer.
Written by Christian Nordqvist