Rare lung cancer: gene activation determines mild or aggressive course
Pulmonary carcinoids are rare tumours of the lung with extremely different clinical courses. In many patients, they behave like benign tumours; surgical removal of the tumour leads to a complete cure. However, some patients experience aggressive growth and spread (metastasis) of the tumour 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 tumours 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.
This study shows for the first time a molecular explanation for the aggressive clinical behavior observed in certain pulmonary carcinoids.
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 unfavourable 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, one of the last authors of the study, is head of the Dept. of Experimental Paediatric Oncology at the University Hospital Cologne) and principal investigator at the Center for Molecular Medicine Cologne at the University of Cologne.
Professor Dr Roman Thomas, director of the Dept. of Translational Genomics and associated principal investigator oof the Center for Molecular Medicine Cologne 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.
Original Publication
TERT Expression and Clinical Outcome in Pulmonary Carcinoids
Lisa Werr, Christoph Bartenhagen , Carolina Rosswog, Maria Cartolano , Catherine Voegele, Alexandra Sexton-Oates , Alex Di Genova, Angela Ernst, Yvonne Kahlert, Nadine Hemstedt, Stefanie Höppner, Audrey Mansuet Lupo, Giuseppe Pelosi, Luka Brcic, Mauro Papotti , Julie George, Graziella Bosco , Alexander Quaas, Laura H Tang, Kenneth Robzyk, Kyuichi Kadota, Mee Sook Roh, Rachel E Fanaroff, Christina J Falcon, Reinhard Büttner, Sylvie Lantuejoul , Natasha Rekhtman, Charles M Rudin, William D Travis, Nicolas Alcala, Lynnette Fernandez-Cuesta, Matthieu Foll, Martin Peifer, Roman K Thomas, Matthias Fischer; Lung NEN Network
J Clin Oncol . 2024 Sep 30:JCO2302708.
doi: 10.1200/JCO.23.02708. Online ahead of print.
https://ascopubs.org/doi/pdf/10.1200/JCO.23.02708
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Dr Graziella Bosco
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Modified press release by CMMC, original press release here