Vall d'Hebron Research Institute identifies new colorectal-tumor suppressor gene

BY BIOCAT

The CIBBIM-Nanomedicine-Molecular Oncology group at the Vall d'Hebron Research Institute (VHIR) has identified the role of a gene (Myosin 1a or MYO1A) in the appearance of colorectal cancer. What until now was seen as a gene with limited importance that is responsible for part of the internal scaffolding of the epithelial cells of the colon (the structure and covering of intestinal follicles) has turned out to be key in tumor development.

This finding shows that MYO1A plays a leading role in colorectal tumors, to the point of making it a supressor gene capable of changing patient survival rates and acting as a prognostic factor. Patients with low levels of the MYO1A protein are disease-free less time and have a shorter survival time (less than one year) when compared to patients with high MYO1A levels in their tumor, who can survive more than nine years. The results of the VHIR’s study were published yesterday in the journal Proceedings of National Academy of Science (PNAS).

"What was looking like a gene with a merely structural role with little importance has been key in the differentiation of the cells of colorectal tumors," explains Dr. Diego Arango, head of this study and of the CIBBIM-VHIR Molecular Oncology group. MYO1A mutations are frequent (found in 32% of all tumors) and, as a result, when this gene is altered and inactivates, epithelial cells lose their ability to differentiate. This leads to low MYO1A levels, increased tumor growth, and a worse prognostic for patients who, thus, have a lower survival rate.

The study, led by the CIBBIM-VHIR Molecular Oncology group with collaboration from other institutions including the CIBER-BBN (CIBER in Bioengineering, Biomaterials and Nanomedicine), Yale University (USA), the Ludwig Institute (Australia), Biomedicum Helsinki (Finland) and Heidelberg University (Germany), was carried out in vitro, searching for the presence of this protein in locally advanced tumor samples, without metastasis but with ganglion affectation (stage III). The analyses were later repeated in animal models in order to characterize the tumor suppression mechanisms and allow researchers to see how high or low levels of MYO1A directly affect tumor development and patient survival. The data was contrasted with the clinical evolution of real colorectal patients, checking the difference in survival rates and period of time patients were disease free.

The results are conclusive: MYO1A is responsible for cell differentiation in colorectal tumors, thus keeping the tumor in check and limiting tumor growth. Low MYO1A levels contribute to accelerated tumor growth. Although this is not the only factor that can lead to a tumor where there wasn’t one previously, it is a key factor in the malignization of colorectal tissue.

This recent finding, for the time being, won’t change the current clinical approach to colorectal tumors. However, Dr. Arango explains that "now we must validate these findings through large studies, but we have firm hopes that identifying this new, important role of the MYO1A gene will help decide which patients with locally advanced colorectal cancer are treated surgically and which are more susceptible to relapse.” This information must be combined with that regarding other markers, but according to the results of the study, if the tumor tissue removed shows low levels of MYO1A “it would be more than justified to be more aggressive with chemotherapy after surgery as the disease will progress in a noteworthy percentage of cases,” affirmed Dr. Arango.