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.
authors.affiliation: Department of Neurological Surgery, University of California-San Francisco, San Francisco, California (K.M.W., J.K.W., A.M.M., M.R.W.); Institute for Human Genetics, University of California-San Francisco, San Francisco, California (J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic, Rochester, Minnesota (D.H.L.); Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California (J.L.W., A.M.M.); Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota (J.E.E.-P.).
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Walsh
authors.affiliation: Department of Neurological Surgery, University of California-San Francisco, San Francisco, California (K.M.W., J.K.W., A.M.M., M.R.W.); Institute for Human Genetics, University of California-San Francisco, San Francisco, California (J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic, Rochester, Minnesota (D.H.L.); Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California (J.L.W., A.M.M.); Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota (J.E.E.-P.).
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.affiliation: Department of Neurological Surgery, University of California-San Francisco, San Francisco, California (K.M.W., J.K.W., A.M.M., M.R.W.); Institute for Human Genetics, University of California-San Francisco, San Francisco, California (J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic, Rochester, Minnesota (D.H.L.); Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California (J.L.W., A.M.M.); Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota (J.E.E.-P.).
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lachance
authors.affiliation: Department of Neurological Surgery, University of California-San Francisco, San Francisco, California (K.M.W., J.K.W., A.M.M., M.R.W.); Institute for Human Genetics, University of California-San Francisco, San Francisco, California (J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic, Rochester, Minnesota (D.H.L.); Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California (J.L.W., A.M.M.); Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota (J.E.E.-P.).
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Wiemels
authors.affiliation: Department of Neurological Surgery, University of California-San Francisco, San Francisco, California (K.M.W., J.K.W., A.M.M., M.R.W.); Institute for Human Genetics, University of California-San Francisco, San Francisco, California (J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic, Rochester, Minnesota (D.H.L.); Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California (J.L.W., A.M.M.); Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota (J.E.E.-P.).
authors.forename: Annette M
authors.initials: AM
authors.lastname: Molinaro
authors.affiliation: Department of Neurological Surgery, University of California-San Francisco, San Francisco, California (K.M.W., J.K.W., A.M.M., M.R.W.); Institute for Human Genetics, University of California-San Francisco, San Francisco, California (J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic, Rochester, Minnesota (D.H.L.); Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California (J.L.W., A.M.M.); Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota (J.E.E.-P.).
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Eckel-Passow
authors.affiliation: Department of Neurological Surgery, University of California-San Francisco, San Francisco, California (K.M.W., J.K.W., A.M.M., M.R.W.); Institute for Human Genetics, University of California-San Francisco, San Francisco, California (J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic, Rochester, Minnesota (D.H.L.); Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California (J.L.W., A.M.M.); Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota (J.E.E.-P.).
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.affiliation: Department of Neurological Surgery, University of California-San Francisco, San Francisco, California (K.M.W., J.K.W., A.M.M., M.R.W.); Institute for Human Genetics, University of California-San Francisco, San Francisco, California (J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic, Rochester, Minnesota (D.H.L.); Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California (J.L.W., A.M.M.); Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota (J.E.E.-P.).
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wrensch
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics*; D005910:Glioma / Q000235:genetics*; D006801:Humans; D016615:Telomere / Q000235:genetics*
keywords: genome-wide association; glioma; shelterin; telomerase; telomere