Telomere maintenance and the etiology of adult glioma

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

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1445-1452
Number of pages8
JournalNeuro-Oncology
Volume17
Issue number11
DOIs
StatePublished - Nov 1 2015

Fingerprint

Telomere
Glioma
Maintenance
Mutation
Telomere Homeostasis
Gene Components
Exome
Neoplasms
Penetrance
Telomerase
Proteins
Leukocytes
Apoptosis

Keywords

  • genome-wide association
  • glioma
  • shelterin
  • telomerase
  • telomere

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Walsh, K. M., Wiencke, J. K., Lachance, D. H., Wiemels, J. L., Molinaro, A. M., Eckel-Passow, J. E., ... Wrensch, M. R. (2015). Telomere maintenance and the etiology of adult glioma. Neuro-Oncology, 17(11), 1445-1452. https://doi.org/10.1093/neuonc/nov082

Telomere maintenance and the etiology of adult glioma. / Walsh, Kyle M.; Wiencke, John K.; Lachance, Daniel H; Wiemels, Joseph L.; Molinaro, Annette M.; Eckel-Passow, Jeanette E; Jenkins, Robert Brian; Wrensch, Margaret R.

In: Neuro-Oncology, Vol. 17, No. 11, 01.11.2015, p. 1445-1452.

Research output: Contribution to journalArticle

Walsh, KM, Wiencke, JK, Lachance, DH, Wiemels, JL, Molinaro, AM, Eckel-Passow, JE, Jenkins, RB & Wrensch, MR 2015, 'Telomere maintenance and the etiology of adult glioma', Neuro-Oncology, vol. 17, no. 11, pp. 1445-1452. https://doi.org/10.1093/neuonc/nov082
Walsh, Kyle M. ; Wiencke, John K. ; Lachance, Daniel H ; Wiemels, Joseph L. ; Molinaro, Annette M. ; Eckel-Passow, Jeanette E ; Jenkins, Robert Brian ; Wrensch, Margaret R. / Telomere maintenance and the etiology of adult glioma. In: Neuro-Oncology. 2015 ; Vol. 17, No. 11. pp. 1445-1452.
@article{5c4bcb4c838f4399a33195d4db957a14,
title = "Telomere maintenance and the etiology of adult glioma",
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",
author = "Walsh, {Kyle M.} and Wiencke, {John K.} and Lachance, {Daniel H} and Wiemels, {Joseph L.} and Molinaro, {Annette M.} and Eckel-Passow, {Jeanette E} and Jenkins, {Robert Brian} and Wrensch, {Margaret R.}",
year = "2015",
month = "11",
day = "1",
doi = "10.1093/neuonc/nov082",
language = "English (US)",
volume = "17",
pages = "1445--1452",
journal = "Neuro-Oncology",
issn = "1522-8517",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - Telomere maintenance and the etiology of adult glioma

AU - Walsh, Kyle M.

AU - Wiencke, John K.

AU - Lachance, Daniel H

AU - Wiemels, Joseph L.

AU - Molinaro, Annette M.

AU - Eckel-Passow, Jeanette E

AU - Jenkins, Robert Brian

AU - Wrensch, Margaret R.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

KW - genome-wide association

KW - glioma

KW - shelterin

KW - telomerase

KW - telomere

UR - http://www.scopus.com/inward/record.url?scp=84946553989&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946553989&partnerID=8YFLogxK

U2 - 10.1093/neuonc/nov082

DO - 10.1093/neuonc/nov082

M3 - Article

C2 - 26014050

AN - SCOPUS:84946553989

VL - 17

SP - 1445

EP - 1452

JO - Neuro-Oncology

JF - Neuro-Oncology

SN - 1522-8517

IS - 11

ER -