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The molecular mechanisms of telomerase reverse transcriptase (<i>TERT)</i> upregulation in breast cancer (BC) are complex. We compared genetic variability within <i>TERT</i> and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the <i>TERT</i>, <i>MYC</i>, <i>TP53</i> and <i>SP1</i> genes in BC patients and in BC organoids (3D cell cultures obtained from breast cancer tissues). We observed the same correlation in the blood of BC patients and in BC organoids between the expression of <i>TERT</i> and <i>TP53</i>. Only in BC patients was a correlation found between the expression of the <i>TERT</i> and <i>MYC</i> genes and between <i>TP53</i> and <i>MYC</i>. We found associations between <i>TERT</i> genotypes (rs2735940 and rs10069690) and <i>TP53</i> expression and telomere length. BC patients with the <i>TT</i> genotype rs2735940 have a shorter telomere length, but patients with <i>A</i> allele rs10069690 have a longer telomere length. BC patients with a short allele VNTR-MNS16A showed higher expression of the <i>SP1</i> and had a longer telomere. Our results bring new insight into the regulation of <i>TERT</i>, <i>MYC</i>, <i>TP53</i> and <i>SP1</i> gene expression related to <i>TERT</i> genetic variability and telomere length. Our study also showed for the first time a similar relationship in the expression of the above genes in BC patients and in BC organoids. These findings suggest that <i>TERT</i> genetic variability, expression and telomere length might be useful biomarkers for BC, but their prognostic value may vary depending on the clinical parameters of BC patients and tumor aggressiveness.