Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies

Abstract

Telomere dynamics play a crucial role in the maintenance of chromosome integrity; changes in telomere length may thus contribute to the development of various diseases including cancer. Understanding the role of telomeric DNA in carcinogenesis and detecting the presence of cell-free telomeric DNA (cf-telDNA) in body fluids offer a potential biomarker for novel cancer screening and diagnostic strategies. Liquid biopsy is becoming increasingly popular due to its undeniable benefits over conventional invasive methods. However, the organization and function of cf-telDNA in the extracellular milieu are understudied. This paper provides a review based on 3,398,017 cancer patients, patients with other conditions, and control individuals with the aim to shed more light on the inconsistent nature of telomere lengthening/shortening in oncological contexts. To gain a better understanding of biological factors (e.g., telomerase activation, alternative lengthening of telomeres) affecting telomere homeostasis across different types of cancer, we summarize mechanisms responsible for telomere length maintenance. In conclusion, we compare tissue- and liquid biopsy-based approaches in cancer assessment and provide a brief outlook on the methodology used for telomere length evaluation, highlighting the advances of state-of-the-art approaches in the field.

The Influence of Telomere-Related Gene Variants, Serum Levels, and Relative Leukocyte Telomere Length in Pituitary Adenoma Occurrence and Recurrence

“…The maintenance of chromosome integrity heavily relies on telomere dynamics. Alterations in telomere length can potentially contribute to the development of cancer [20]. Leukocyte telomere length is known to be heritable and has been associated with longevity.…”

Blastocyst telomere length predicts successful implantation after frozen-thawed embryo transfer

“…Telomeres are known to control cell division and cellular death; thus playing a critical role in cell maintenance and chromosome integrity ( Bernadotte et al , 2016 ). Previous studies have shown that TL is a biomarker for various human diseases and pathological conditions such as coronary artery disease ( Sagris et al , 2022 ), diabetic kidney disease ( Hill et al , 2023 ), exposure to air pollution ( Zizza et al , 2022 ), and cancers ( Holesova et al , 2023 ). Furthermore, TL is essential in normal development of the embryo and fetus; thus, the abnormal shortening of telomeres is likely involved in embryo loss during early human development ( Thilagavathi et al , 2013 ; Kohlrausch et al , 2021 ) and is the primary indicator of non-viable fetus elimination ( Huleyuk et al , 2018 ).…”

Genetically predicted telomere length and the risk of 11 hematological diseases: a Mendelian randomization study

“…In fact, several scholars have suggested that both shorter and longer telomeres may contribute to carcinogenesis, and that an optimal TL represented a balance between cell proliferation, senescence, and control [41][42][43]. Cells with longer TL had greater proliferative and mutational potential, leading to the onset of HODGKIN, while shortened TL was often correlated with disease severity after onset [44,45].…”