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.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Walsh KM,Wiencke JK,Lachance DH,Wiemels JL,Molinaro AM,Eckel-Passow JE,Jenkins RB,Wrensch MRdoi
10.1093/neuonc/nov082subject
Has Abstractpub_date
2015-11-01 00:00:00pages
1445-52issue
11eissn
1522-8517issn
1523-5866pii
nov082journal_volume
17pub_type
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