Background: Telomere maintenance has been proposed as an essential step for tumor cell immortalization. The objectives of the current study were to investigate the mechanisms implicated in telomere length in colorectal carcinoma (CRC) and to evaluate the prognostic impact of telomere status.
Methods: Ninety-one colorectal carcinoma samples that were obtained from patients who underwent surgery were analyzed to investigate the factors related to telomere function. The authors studied telomerase activity, terminal restriction fragment (TRF) length, and telomeric-repeat binding factor (TRF1) expression and analyzed the prognostic implications of those factors.
Results: Most tumors (81.3%) displayed telomerase activity. Overall, telomeres in CRC specimens were significantly shorter compared with telomeres in normal, adjacent specimens (P=0.02). Moreover, tumors that demonstrated shortened telomeres displayed higher TRF1 levels than tumors without telomere shortening. In relation to patient prognosis, a significantly poor clinical course was observed in the group of patients who had tumors with longer telomeres (P=0.02), and this finding emerged as an independent prognostic factor in a Cox proportional hazards model (P=0.04; relative risk, 6.48). Among patients with tumors classified as telomerase-positive, telomere length ratios (the ratio of tumor tissues to normal tissues)
Conclusions: The majority of CRC specimens in the current study displayed telomerase reactivation. However, only those tumors that displayed telomere elongation conferred a poor prognosis. Conversely, colorectal tumors that over-expressed TRF1 demonstrated telomere shortening, and patients with those tumors had a better clinical course.
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http://dx.doi.org/10.1002/cncr.21625 | DOI Listing |
J Aging Health
January 2025
Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Objectives: To examine the association of social connections with blood leukocyte telomere length (LTL) and all-cause mortality in older Costa Ricans.
Methods: Utilizing data from the Costa Rican Longevity and Healthy Aging Study (CRELES), a prospective cohort of 2827 individuals aged 60 and above followed since 2004, we constructed a Social Network Index (SNI) based on marital status, household size, interaction with non-cohabitating adult children, and church attendance. We used linear regression to assess SNI's association with baseline LTL ( = 1113), and Cox proportional-hazard models to examine SNI's relationship with all-cause mortality ( = 2735).
Sci Rep
January 2025
Department of Thoracic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
Non-small cell lung cancer (NSCLC), half of which are lung adenocarcinoma (LUAD), is one of the most widely spread cancers in the world. Telomerase, which maintains telomere length and chromosomal integrity, enables cancer cells to avoid replicative senescence. When telomerase is inhibited, cancer cells' senescence began, preventing them from growing indefinitely.
View Article and Find Full Text PDFNat Genet
January 2025
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult to resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 human genome assemblies (from 85 samples representing 38 Africans and 47 non-Africans) in which the majority of autosomal SDs are fully resolved using long-read sequence assembly. Excluding the acrocentric short arms and sex chromosomes, we identify 173.
View Article and Find Full Text PDFBiogerontology
January 2025
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 210, 171 77, Stockholm, Sweden.
Biomarkers of ageing (BA) can predict health risks beyond chronological age, but little is known about how marital/living status affects longitudinal changes in BA. We examined the association between marital/living status and BA over time using the-Swedish-Adoption/Twin-Study-of-Aging (SATSA) cohort. Four BAs were analyzed: telomere length (TL) (638 individuals; 1603 measurements), DNAmAge (535 individuals; 1392 measurements), cognition (823 individuals; 3218 measurements), and frailty index (FI) (1828 individuals; 9502 measurements).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Département de Biologie, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms. In 10 to 15% of cancers, this is enabled by recombination-based alternative lengthening of telomeres pathways (ALT). ALT cells display several hallmarks including heterogeneous telomere length, extrachromosomal telomeric repeats, and ALT-associated PML bodies.
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