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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas
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TERT Expression and Clinical Outcome in Pulmonary Carcinoids.

Lisa Werr1,2, Christoph Bartenhagen1,2, Carolina Rosswog1,2,3

  • 1Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Cologne, Germany.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|September 30, 2024
PubMed
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High telomerase reverse transcriptase (TERT) expression in pulmonary carcinoids indicates aggressive disease and poor survival. This finding, similar to neuroblastoma, suggests TERT activation is key in lethal cancers.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Pulmonary carcinoids exhibit a wide clinical spectrum, from indolent to fatal.
  • Specific molecular alterations are suspected to drive malignant progression in pulmonary carcinoids.
  • Activation of telomerase reverse transcriptase (TERT) is a critical factor in pediatric neuroblastoma progression.

Purpose of the Study:

  • To investigate if TERT expression levels can predict the clinical outcome of pulmonary carcinoid tumors.
  • To determine if TERT expression serves as a prognostic marker for pulmonary carcinoid patients.

Main Methods:

  • TERT expression was quantified using RNA sequencing in two independent cohorts of pulmonary carcinoids (n=88 and n=105).
  • A natural cutoff for TERT expression was established to stratify tumors into high and low expression groups.
  • Prognostic value was assessed using Kaplan-Meier survival analysis and multivariable models; telomerase activity was confirmed via telomere repeat amplification protocol assay.

Main Results:

  • Pulmonary carcinoid tumors displayed a bimodal distribution of TERT expression, creating distinct TERT-high and TERT-low subgroups.
  • A defined TERT expression cutoff accurately differentiated between unfavorable and favorable clinical courses in both cohorts.
  • High TERT expression was identified as an independent prognostic marker for poor survival, with a hazard ratio of 5.243 (95% CI, 1.943 to 14.148; P = .001).
  • Telomerase activity correlated with TERT expression levels, being largely absent in TERT-low tumors and detectable in TERT-high tumors.

Conclusions:

  • High TERT expression is a defining characteristic of clinically aggressive pulmonary carcinoids with a fatal outcome.
  • The findings suggest that TERT activation may be a crucial determinant in the lethality of various cancers, including pulmonary carcinoids.
  • TERT expression serves as a significant prognostic indicator for pulmonary carcinoid patients.