Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer

Abstract

The molecular mechanisms of telomerase reverse transcriptase (TERT) upregulation in breast cancer (BC) are complex. We compared genetic variability within TERT and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the TERT, MYC, TP53 and SP1 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 TERT and TP53. Only in BC patients was a correlation found between the expression of the TERT and MYC genes and between TP53 and MYC. We found associations between TERT genotypes (rs2735940 and rs10069690) and TP53 expression and telomere length. BC patients with the TT genotype rs2735940 have a shorter telomere length, but patients with A allele rs10069690 have a longer telomere length. BC patients with a short allele VNTR-MNS16A showed higher expression of the SP1 and had a longer telomere. Our results bring new insight into the regulation of TERT, MYC, TP53 and SP1 gene expression related to TERT 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 TERT 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.

Parental Genetics Communicate with Intrauterine Environment to Reprogram Newborn Telomeres and Immunity

“…Molecular disruptions, such as mutation or genetic variation in both TERT along with p53 gene, can alter expression and often lead to aberrant telomerase activation that can induce uncontrolled cell proliferation and miss the DNA repair process, causing oncogenesis [ 32 ]. A meta-analysis highlighted that the TERT SNP rs2736100 of C allele is associated with multiple cancerous diseases, whereas the A allele is associated with a predisposition to especially degenerative noncancerous diseases [ 33 ].…”

No evident causal association between Helicobacter pylori infection and colorectal cancer: a bidirectional mendelian randomization study

“…rs11213823C maps to the colorectal cancer-associated 2 gene (COLCA2), which has been identified as being causally associated with the increased risk of CRC 32 . Shorter telomeres 33 and increased cancer risk 34 have been associated with the human telomerase reverse transcriptase gene and its related SNP, rs2735940G. Unfortunately, little information and few related publications are currently available on the SNPs rs16969344G, rs2337113G, and rs7897408G.…”

Telomere length and hTERT genetic variants as potential prognostic markers in multiple myeloma

“…The current knowledge of human cancer development shows that telomere dysfunction may be a key event causing genomic instability and disease progression in many types of solid tumours e.g. renal cell carcinoma 22 , glioma 23 , 24 , esophageal squamous cell carcinoma 25 , gastric cancer 26 , ovarian and breast cancer 27 – 30 . Additionally, telomere shortening has also been observed in haematological malignancies, both acute and chronic leukaemias 31 – 34 , some lymphomas 35 – 37 , as well as bone marrow failure syndromes (myelodysplastic syndrome (MDS)) 38 , 39 and aplastic anaemia 40 – 42 .…”

“…In addition, SNPs can affect telomere length, as their variants can modulate the expression of a broad spectrum of genes e.g. Myc , TP53 and NFKB 30 , 54 , 55 . For example, − 1327C>T (rs2735940) is a SNP located in the promoter region of h TERT gene (h TERT p) and is a T/C transition 1327-bp upstream of the transcription start site and is able to induce expression of h TERT by upregulating its transcriptional activity in vitro and h TERT mRNA expression in vivo 53 .…”