Article

Familial Cancer

, Volume 9, Issue 3, pp 413-421

First online:

Survey of familial glioma and role of germline p16 INK4A /p14 ARF and p53 mutation

  • Lindsay B. RobertsonAffiliated withSection of Cancer Genetics, Institute of Cancer Research (ICR)
  • , Georgina N. ArmstrongAffiliated withDepartment of Epidemiology, M.D. Anderson Cancer Center (MDACC), The University of Texas
  • , Bianca D. OlverAffiliated withSection of Cancer Genetics, Institute of Cancer Research (ICR)
  • , Amy L. LloydAffiliated withSection of Cancer Genetics, Institute of Cancer Research (ICR)
  • , Sanjay SheteAffiliated withDepartment of Epidemiology, M.D. Anderson Cancer Center (MDACC), The University of Texas
  • , Ching LauAffiliated withBaylor College of Medicine, Texas Children’s Cancer Center (TCH)
  • , Elizabeth B. ClausAffiliated withDepartment of Epidemiology and Public Health, Yale University School of MedicineDepartment of Neurosurgery, Brigham and Women’s Hospital Boston (BW)
  • , Jill Barnholtz-SloanAffiliated withCase Comprehensive Cancer Center, Case Western Reserve University School of Medicine
  • , Rose LaiAffiliated withThe Neurological Institute of Columbia University
    • , Dora Il’yasovaAffiliated withCancer Control and Prevention Program, Department of Community and Family Medicine, Duke University Medical Center
    • , Joellen SchildkrautAffiliated withCancer Control and Prevention Program, Department of Community and Family Medicine, Duke University Medical Center
    • , Jonine L. BernsteinAffiliated withDepartment of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Centre (MSK)
    • , Sara H. OlsonAffiliated withDepartment of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Centre (MSK)
    • , Robert B. JenkinsAffiliated withMayo Comprehensive Clinic Cancer, Mayo Clinic
    • , Ping YangAffiliated withMayo Comprehensive Clinic Cancer, Mayo Clinic
    • , Amanda L. RynerasonAffiliated withMayo Comprehensive Clinic Cancer, Mayo Clinic
    • , Margaret WrenschAffiliated withDepartment of Neurological Surgery, University of California, San Francisco (UCSF)
    • , Lucie McCoyAffiliated withDepartment of Neurological Surgery, University of California, San Francisco (UCSF)
    • , John K. WienkceAffiliated withDepartment of Neurological Surgery, University of California, San Francisco (UCSF)
    • , Bridget McCarthyAffiliated withDivision of Epidemiology and Biostatistics, University of Illinois at Chicago (UIC)
    • , Faith DavisAffiliated withDivision of Epidemiology and Biostatistics, University of Illinois at Chicago (UIC)
    • , Nicholas A. VickAffiliated withDepartment of Neurology, NorthShore University HealthSystem
    • , Christoffer JohansenAffiliated withInstitute of Cancer Epidemiology, Danish Cancer Society
    • , Hanne BødtcherAffiliated withInstitute of Cancer Epidemiology, Danish Cancer Society
    • , Siegal SadetzkiAffiliated withCancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center
    • , Revital Bar-Sade BruchimAffiliated withDepartment of Neurosurgery, Tel-Aviv Sourasky Medical Center
    • , Galit Hirsh YechezkelAffiliated withSackler School of Medicine, Tel-Aviv University
    • , Ulrika AnderssonAffiliated withDepartment of Radiation Sciences Oncology, Umeå University
    • , Beatrice S. MelinAffiliated withDepartment of Radiation Sciences Oncology, Umeå University
    • , Melissa L. BondyAffiliated withDepartment of Epidemiology, M.D. Anderson Cancer Center (MDACC), The University of Texas
    • , Richard S. HoulstonAffiliated withSection of Cancer Genetics, Institute of Cancer Research (ICR) Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

There is increasing recognition of familial propensity to glioma as a distinct clinical entity beyond a few rare syndromes; however its genetic basis is poorly understood. The role of p16 INK4A /p14 ARF and p53 mutations in sporadic glioma provides a strong rationale for investigating germline mutations in these genes as a cause of familial glioma. To survey the familial glioma phenotype and examine the contribution of germline mutation in p16 INK4A /p14 ARF and p53 to the disease we have analyzed a series of 101 index familial cases collected through the GLIOGENE Consortium (http://​braintumor.​epigenetic.​org/​). There was little evidence for within family correlations for tumour histology, suggesting generic susceptibility to glial tumors. We did not detect any functional mutations in p16 INK4A or p14 ARF . One index case with glioblastoma multiforme (GBM) diagnosed at age 54 and had a family history comprised of a paternal aunt with GBM at age 55, carried the p53 R158H mutation, which is predicted to be functional and has previously been implicated as a cause of Li-Fraumeni syndrome. Our findings provide no evidence that p16 INK4A /p14 ARF and p53 mutations contribute significantly to familial glioma.

Keywords

p16INK4A/p14ARF p53 Mutation Familial glioma