hTERT DNA Methylation Analysis Identifies a Biomarker for Retinoic Acid-Induced hTERT Repression in Breast Cancer Cell Lines

Telomerase reactivation is responsible for telomere preservation in about 90% of cancers, providing cancer cells an indefinite proliferating potential. Telomerase consists of at least two main subunits: a catalytic reverse transcriptase protein (hTERT) and an RNA template subunit. Strategies to inhibit hTERT expression seem promising for cancer treatment. Previous works showed that all-trans retinoic acid (ATRA) induces hTERT repression in acute promyelocytic leukemia cells, resulting in their death. Here, we investigated the effects of ATRA in a subset of breast cancer cell lines. The mutational status of hTERT promoter and the methylation patterns at a single CpG resolution were assessed. We observed an inverse relationship between hTERT expression after ATRA treatment and the methylation level of a specific CpG at chr5: 1,300,438 in a region of hTERT gene at -5 kb of the transcription initiation site. This observation highlighted the significance of this region, whose methylation profile could represent a promising biomarker to predict the sensitivity to ATRA-induced hTERT repression in specific breast cancer subtypes. As hTERT repression promotes drug-induced cell death, checking the methylation status of this unique region and the specific CpG included can help in decision-making to include ATRA in combination therapy and contributes to a better clinical outcome.