Here Comes the Sun – TERT Promoter Mutations in Skin Lesions

Summer has arrived in Amsterdam and many other parts of the northern hemisphere, bringing long days and bright sunshine. While we enjoy the warmth, it’s also a timely reminder of the importance of protecting our skin from harmful UV exposure.

Prolonged UV exposure is a known risk factor for skin cancer, and when lesions appear and when these present a certain clinical profile, testing for TERT promoter mutations can provide valuable insights into the nature of the neoplasm. These point mutations are among the earliest genetic alterations observed in the development of malignant skin lesions (Shain et al. 2015).

However, detecting TERT promoter mutations is technically challenging when using standard PCR and NGS methods, due to the region’s high GC content—often exceeding 80%—which can lead to poor read depth or even false negatives.

Thanks to the unique design of mutation-specific MLPA probes, these detection challenges can be effectively circumvented. For instance, two of the most common TERT promoter mutations—C228T and C250T—can be detected using the P105 Glioma and ME012 MGMT-IDH-TERT probemixes.

The P105 Glioma probemix also includes probes for detecting CDKN2A deletions, which are often biallelic and may serve as markers of invasiveness in various neoplasms, including skin lesions (Shain et al. 2015).