Gene activation linked to severity of a rare lung cancer

Pulmonary carcinoids are rare tumors of the lung with extremely different clinical courses. In many patients, they behave like benign tumors; surgical removal of the tumor leads to a complete cure. However, some patients experience aggressive growth and spread (metastasis) of the tumor with poor chances of recovery. The biological causes of these different forms of the disease are still unknown.

In a joint study, researchers from the Experimental Paediatric Oncology Department at University Hospital Cologne and the Department of Translational Genomics at the University of Cologne have now discovered that the progression of pulmonary carcinoid tumors is linked to activation of the TERT (telomerase reverse transcriptase) gene. The study “TERT Expression and Clinical Outcome in Pulmonary Carcinoids” has been published in the Journal of Clinical Oncology.

“Our study for the first time found a molecular explanation for the aggressive clinical behavior we observe in certain pulmonary carcinoids,” said first author Dr. Lisa Werr.

The TERT gene is responsible for the production of telomerase, a protein that contributes significantly to the stabilization of chromosome ends (telomeres). This enzyme is not active in most healthy body cells, which limits the cells’ ability to divide. In stem cells and cancer cells, however, the activation of telomerase leads to an unlimited ability to divide, making these cells immortal and allowing them to grow indefinitely.

The researchers found that clinically aggressive pulmonary carcinoids are characterized by activation of the TERT gene, while telomerase is not activated in carcinoids with a benign course. They had previously made a similar observation with neuroblastoma, a common type of cancer in children: The unfavorable clinical course of this type of cancer was also dependent on the presence of telomere stabilization mechanisms.

“The findings of this study will make it possible to predict the course of the disease more accurately in future and therefore also to plan the intensity of treatment according to individual needs,” said Professor Dr. Matthias Fischer, head of the Department of Experimental Paediatric Oncology at University Hospital Cologne and one of the two last authors of the study.

Professor Dr. Roman Thomas, director of the Department of Translational Genomics at the University of Cologne, added, “The results also show that the activation of telomere stabilization mechanisms is a key feature of malignant cancers that distinguishes them from benign tumors. The development of targeted therapeutic strategies against telomere stabilization mechanisms could therefore improve the treatment of many cancer types in the future.”