New collaborative publication in JCO

The clinical course of pulmonary carcinoids ranges from curable tumors to lethal variants, suggesting that specific molecular alterations drive progression toward the fully malignant state. The biological determinants of the diverse clinical phenotypes, however, have remained unclear to date.

In a collaborative study, published today in the Journal of Clinical Oncology, researchers from the Department of Experimental Pediatric Oncology, in the University Children’s Hospital, and the Department of Translational Genomics, both at the University of Cologne, have discovered that induction of the gene TERT, encoding for telomerase reverse transcriptase, is a defining feature of the aggressive variant of pulmonary carcinoids. Telomerase is an enzyme that is essential for stabilizing the ends of the chromosomes, the telomeres. Normal cells, lack telomerase, which limits their capacity to replicate. By contrast, cancerous cells frequently regain telomerase activity, which thus confers replicative immortality.

The scientists  found that pulmonary carcinoids with poor clinical outcome are characterized by induction of TERT expression and telomerase activity, while telomerase activity was absent in carcinoids with favorable outcome. These findings are in line with previous observations in pediatric neuroblastoma, in which a deadly course of disease is also driven by the presence of telomere maintenance mechanisms.

The results of the current study will allow to more accurately predict the course of disease in patients with pulmonary carcinoids, which will enable tailoring of treatment intensities according to the individual patient risk. More broadly, the results highlight activation of telomere maintenance as a key feature of lethal cancers, making telomerase an attractive therapeutic target for development of novel cancer medicines.

Werr L, Bartenhagen C, Rosswog C, Cartolano M, Voegele C, Sexton-Oates A, Di Genova A, ErnstA, Kahlert Y, Hemstedt N, Höppner S, Mansuet Lupo A, Pelosi G, BrcicL, Papotti M, George J, Bosco G, Quaas A, Tang LH, Robzyk K, Kadota K, Roh MS, Fanaroff RE, Falcon CJ, Büttner R, Lantuejoul S, Rekhtman N, Rudin CM, Travis WD, Alcala N, Fernandez-Cuesta L, Foll M, Peifer M, Thomas RK, Fischer M.

TERT expression and clinical outcome in pulmonary carcinoids. J Clin Oncol 2024, doi.org/10.1200/JCO.23.02708