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Review
. 2015 Nov;17(11):1445-52.
doi: 10.1093/neuonc/nov082. Epub 2015 May 25.

Telomere maintenance and the etiology of adult glioma

Kyle M Walsh  1 , John K Wiencke  1 , Daniel H Lachance  1 , Joseph L Wiemels  1 , Annette M Molinaro  1 , Jeanette E Eckel-Passow  1 , Robert B Jenkins  1 , Margaret R Wrensch  1
Affiliations
Review

Telomere maintenance and the etiology of adult glioma

Kyle M Walsh et al. Neuro Oncol. 2015 Nov.

Abstract

A growing body of epidemiologic and tumor genomic research has identified an important role for telomere maintenance in glioma susceptibility, initiation, and prognosis. Telomere length has long been investigated in relation to cancer, but whether longer or shorter telomere length might be associated with glioma risk has remained elusive. Recent data address this question and are reviewed here. Common inherited variants near the telomerase-component genes TERC and TERT are associated both with longer telomere length and increased risk of glioma. Exome sequencing of glioma patients from families with multiple affected members has identified rare inherited mutations in POT1 (protection of telomeres protein 1) as high-penetrance glioma risk factors. These heritable POT1 mutations are also associated with increased telomere length in leukocytes. Tumor sequencing studies further indicate that acquired somatic mutations of TERT and ATRX are among the most frequent alterations found in adult gliomas. These mutations facilitate telomere lengthening, thus bypassing a critical mechanism of apoptosis. Although future research is needed, mounting evidence suggests that glioma is, at least in part, a disease of telomere dysregulation. Specifically, several inherited and acquired variants underlying gliomagenesis affect telomere pathways and are also associated with increased telomere length.

Keywords: genome-wide association; glioma; shelterin; telomerase; telomere.

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Figures

Fig. 1.
Fig. 1.
Hypothesized pathways of glioma development, highlighting heritable and somatic genetic variants. From left to right: gene regions that contribute inherited risk for all histopathologic classifications of glioma. Gene regions that contribute inherited risk for specific histopathologic classifications of glioma. Somatic (ie, acquired) genetic changes that are believed to be early events in the development of glioma. Additional somatic events important for malignant progression. Gene names appearing in green font harbor glioma risk alleles associated with telomere lengthening. (Figure created with assistance from Xavier Studio.)
See this image and copyright information in PMC

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References

    1. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–466. - PubMed
    1. Walsh KM, Codd V, Smirnov IV, et al. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. Nat Genet. 2014;46(7):731–735. - PMC - PubMed
    1. Wrensch M, Jenkins RB, Chang JS, et al. Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet. 2009;41(8):905–908. - PMC - PubMed
    1. Shete S, Hosking FJ, Robertson LB, et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet. 2009;41(8):899–904. - PMC - PubMed
    1. Sanson M, Hosking FJ, Shete S, et al. Chromosome 7p11.2 (EGFR) variation influences glioma risk. Hum Mol Genet. 2011;20(14):2897–2904. - PMC - PubMed

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