Expression of TERT (AS) alternative splicing variants and TERF2 in osteosarcoma

Expression of TERT (AS) alternative splicing variants and TERF2 in osteosarcoma

Authors

  • Indhira Dias Oliveira 1- Pediatric Oncology Institute/GRAACC, Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil 2- Department of Morphology and Genetics, Division of Genetics, Federal University of São Paulo, São Paulo, SP, Brazil
  • Antonio Sergio Petrilli Pediatric Oncology Institute/GRAACC, Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil
  • Carla Renata Pacheco Donato Macedo Pediatric Oncology Institute/GRAACC, Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil
  • Maria Teresa de Seixas Alves 1- Pediatric Oncology Institute/GRAACC, Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil 2- Department of Pathology, Federal University of São Paulo, São Paulo, SP, Brazil
  • Reinaldo de Jesus Garcia Filho 1- Pediatric Oncology Institute/GRAACC, Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil 2- Department of Orthopaedics and Traumathology, Federal University of São Paulo, São Paulo, SP, Brazil
  • Silvia Regina Caminada Toledo 1- Pediatric Oncology Institute/GRAACC, Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil 2- Department of Morphology and Genetics, Division of Genetics, Federal University of São Paulo, São Paulo, SP, Brazil

Keywords:

pediatric osteosarcoma, telomere maintenance, TERT, alternative splicing variants, TERC, TERF1, TERF2, gene expression, molecular marker

Abstract

Background: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Mechanisms of telomere maintenance (TMM) are central features of the tumor cells to maintaining their proliferative capacity. Aim: In this study, we investigated the expression of TERT (telomerase reverse transcriptase) alternative splicing (AS) variants, TERC (telomerase RNA component), TERF1 (telomeric repeat binding factor 1) and TERF2 (telomeric repeat binding factor 2) and quantified telomerase enzyme activity in samples of OS, correlating with clinical and pathological aspects. Methods: A total of 70 fragments of OS tumor samples and 10 normal bone samples (NB) were used for the analysis of gene expression by nested RT-PCR (reverse transcriptase-polymerase chain reaction) and qPCR (quantitative real time PCR). For the quantification of telomerase by TRAP assay we used 20 OS samples and two NB samples. Results: We observed the expression of TERT in 44% of the tumors and full length (FL) isoform in only 4%. TERF2 expression levels were higher in PRECH (pre-chemotherapy) samples than in POSTCH (post-chemotherapy) (p= 0.0468). POSTCH samples from patients without relapse showed lower levels of expression of TERF2 (p= 0.0167). Conclusions: Despite the high expression of TERC, the low prevalence of isoform FL suggested that telomerase may not be the main TMM in OS. Recent studies have correlated TERF2 overexpression to different mechanisms of resistance to chemotherapeutic drugs. Low levels of TERF2 gene expression, in POSTCH samples from patients with no relapse of disease suggest a correlation with a better response to treatment. 

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Published

2017-02-20

Issue

European Journal of Oncology Vol.21, No 4 (2016)

Section

Research

License

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How to Cite

1.
Dias Oliveira I, Petrilli AS, Macedo CRPD, de Seixas Alves MT, Filho R de JG, Toledo SRC. Expression of TERT (AS) alternative splicing variants and TERF2 in osteosarcoma. Eur J Oncol Env Hea [Internet]. 2017 Feb. 20 [cited 2025 Apr. 4];21(4):227-3. Available from: https://mattioli1885journals.com/index.php/EJOEH/article/view/4340

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