scholarly journals Telomere length in peripheral blood lymphocytes related to genetic variation in telomerase, prognosis and clinicopathological features in breast cancer patients

Mutagenesis ◽  
2020 ◽  
Author(s):  
Michal Kroupa ◽  
Sivaramakrishna Rachakonda ◽  
Veronika Vymetalkova ◽  
Kristyna Tomasova ◽  
Vaclav Liska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Telomere Length ◽  
Peripheral Blood ◽  
Quantitative Polymerase Chain Reaction ◽  
Peripheral Blood Lymphocytes ◽  
Clinicopathological Features ◽  
Genome Wide Association Studies ◽  
Healthy Controls ◽  
Blood Lymphocytes ◽  
Potential Biomarker

Abstract Disruption of telomere length (TL) homeostasis in peripheral blood lymphocytes has been previously assessed as a potential biomarker of breast cancer (BC) risk. The present study addressed the relationship between lymphocyte TL (LTL), prognosis and clinicopathological features in the BC patients since these associations are insufficiently explored at present. LTL was measured in 611 BC patients and 154 healthy controls using the monochrome multiplex quantitative Polymerase Chain Reaction assay. In addition, we genotyped nine TL-associated single-nucleotide polymorphisms that had been identified through genome-wide association studies. Our results showed that the patients had significantly (P = 0.001, Mann–Whitney U-test) longer LTL [median (interquartile range); 1.48 (1.22–1.78)] than the healthy controls [1.27 (0.97–1.82)]. Patients homozygous (CC) for the common allele of hTERT rs2736108 or the variant allele (CC) of hTERC rs16847897 had longer LTL. The latter association remained statistically significant in the recessive genetic model after the Bonferroni correction (P = 0.004, Wilcoxon two-sample test). We observed no association between LTL and overall survival or relapse-free survival of the patients. LTL did not correlate with cancer staging based on Union for International Cancer Control (UICC), The tumor node metastasis (TNM) staging system classification, tumour grade or molecular BC subtypes. Overall, we observed an association between long LTL and BC disease and an association of the hTERC rs16847897 CC genotype with increased LTL. However, no association between LTL, clinicopathological features and survival of the patients was found.

Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls

2010 ◽  
Vol 31 (7) ◽  
pp. 1238-1241 ◽  
Author(s):  
P. Vodicka ◽  
Z. Polivkova ◽  
S. Sytarova ◽  
H. Demova ◽  
M. Kucerova ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Chromosomal Damage ◽  
Blood Lymphocytes

scholarly journals The telomere length of gastric mucosal samples and peripheral blood lymphocytes in patients who have undergone Billroth II distal gastrectomy

2020 ◽  
Vol 16 (3) ◽  
pp. 577-583
Author(s):  
Muge Ustaoglu ◽  
Ahmet Bektas ◽  
Abdulkerim Bedir ◽  
Tulay Bakir ◽  
Aynur Duzgun ◽  
...  
Keyword(s):  
Telomere Length ◽  
Peripheral Blood ◽  
Distal Gastrectomy ◽  
Peripheral Blood Lymphocytes ◽  
Billroth Ii ◽  
Blood Lymphocytes

scholarly journals Replication Timing Aberrations and Aneuploidy in Peripheral Blood Lymphocytes of Breast Cancer Patients

Neoplasia ◽  
2010 ◽  
Vol 12 (8) ◽  
pp. 668-674 ◽  
Author(s):  
Helena Grinberg-Rashi ◽  
Samuel Cytron ◽  
Zully Gelman-Kohan ◽  
Talia Litmanovitch ◽  
Lydia Avivi
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Replication Timing ◽  
Peripheral Blood Lymphocytes ◽  
Breast Cancer Patients ◽  
Blood Lymphocytes

Telomeric Recombination in Lymphocytes Implicates ALT, an Alternative Mechanism for Telomere Length Maintenance, in Normal Human Hematopoietic Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1332-1332
Author(s):  
Rodrigo T. Calado ◽  
Solomon A. Graf ◽  
Neal S. Young
Keyword(s):  
Telomere Length ◽  
Sister Chromatid ◽  
Hela Cells ◽  
Peripheral Blood ◽  
Sister Chromatid Exchange ◽  
Mammalian Cells ◽  
K562 Cells ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes ◽  
Telomeric Probe

Abstract Telomeres are the very ends of chromosomes and protect the genome from recombination, end-to-end-fusion, and recognition as damaged DNA. Telomeres are eroded with each cell division, eventually reaching such critically short length as to cause cell cycle arrest, apoptosis, or genomic instability. In most highly proliferative cells, including hematopoietic stem cells and T lymphocytes, telomere attrition is countered by telomere extension by telomerase reverse transcriptase complex. The majority of cancer cells also express telomerase, which maintains telomere length and allows indefinite cell proliferation. However, about 10% of tumors maintain telomere length in the absence of telomerase by mechanisms collectively termed alternative lengthening of telomeres (ALT). ALT mainly acts through asymmetrical exchange of telomeric material between chromosomes or sister chromatids, producing one daughter-cell with short telomeres and a limited life-span and its sister with long telomeres and higher proliferative capacity. To date, ALT has only been reported in cancer cells or through genetic engineering of mammalian cells. Here we investigated whether ALT mechanisms were active in hematopoietic cells using chromosome orientation fluorescent in situ hybridization (CO-FISH). In standard FISH, a telomeric probe produces fours signals per chromosome, one at each end of the two chromatids. Using CO-FISH, the newly synthesized DNA strand is fragmented by BrdU incorporation and UV light exposure and then digested by exonucleases. In CO-FISH, a telomeric probe produces two signals only, one at each end of the chromosome; in the presence of telomeric recombination, the telomeric signal is split, generating more than two signals per chromosome. Peripheral blood lymphocytes from three healthy volunteers, normal human fibroblasts, K562 cells, telomerase-positive HeLa cells (known to be negative for ALT),and telomerase-negative VA13 cells (known to be positive for ALT) were investigated for telomeric sister chromatid exchange (t-SCE); at least 20 metaphases per cell type were examined. Cultured peripheral blood lymphocytes and VA13 cells both showed increased levels of telomeric sister chromatid exchange in comparison to the other cells (P=0.0001): telomeric probe generated 2.62±0.11 telomeric signals/chromosome in lymphocytes; 2.23±0.04 in VA13 cells; 2.09±0.01 in HeLa cells; 2.02±0.01 in K562 cells; and 2.02±0.01 in human skin fibroblasts. Staining incorporated-BrdU over 24 hours and evaluation of “harlequin” chromosomes point to a similar rate of genomic sister chromatid exchange in lymphocytes, VA13 cells, and HeLa cells, suggesting that high chromatid exchange is confined to the telomeric region. A physical association between promyelocytic leukemia protein (PML) and telomeres is characteristic of some ALT-positive cells, but confocal microscopy failed to co-localize the telomeric probe and anti-PML monoclonal antibody in peripheral blood lymphocytes, suggesting that t-SCE in lymphocytes is not mediated by PML. This is the first demonstration of ALT activation in normal mammalian cells. ALT may be activated in peripheral blood lymphocytes as a complementary mechanism to maintain telomere length, and may explain the differences in age-related telomere shortening observed between lymphocytes and granulocytes.

scholarly journals Methylomic alteration in peripheral blood lymphocytes of prodromal stage and first-episode Chinese Han schizophrenia patients

2021 ◽  
Author(s):  
Yi Liu ◽  
Bing Lang ◽  
Robert C. Smith ◽  
Guodong Wang ◽  
Jijun Wang ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Chinese Han Population ◽  
First Episode ◽  
Healthy Controls ◽  
Chinese Han ◽  
Han Population ◽  
Blood Lymphocytes ◽  
Psychosis Risk ◽  
First Episode Schizophrenia

AbstractBackgroundAlthough epigenetic dysregulation has long been proposed to promote the onset of schizophrenia, the landscape of the methylomic changes across the whole genome is yet established.MethodsUsing Infinium Human Methylation 850 BeadChip Array and MethylTarget sequencing method, we investigated the genome-wide methylation profiles and further validated methylation profiles of target genes in peripheral blood lymphocytes between individuals with psychosis risk syndrome (PRS), patients with first-episode schizophrenia (FES) and healthy controls (HC) in Chinese Han population.ResultsWe detected 372 sites between psychosis risk syndrome (PRS) and healthy controls (HC), which increased to 460 sites in first-episode schizophrenia (FES) with 207 sites shared. Both PRS and FES featured profound hypomethylation within gene body. Gene ontology and network annotation merged on loci enriched in disease associated signaling pathways (MAPK(Mitogen Activated Protein Kinases), Glutamatergic, GABAergic etc.).ConclusionsOur study implicated characteristic hypomethylation in both the discovery and validation cohorts in SYNGAP1, one of the frequently studied genes in neurodevelopmental disorders. This is the first methylome-wide association study between PRS and FES in Chinese Han population. Our findings provide potential biomarkers that can be used for future development of disease therapy and management.

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