Familial Cancer

, Volume 9, Issue 3, pp 413–421

Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation

  • Lindsay B. Robertson
  • Georgina N. Armstrong
  • Bianca D. Olver
  • Amy L. Lloyd
  • Sanjay Shete
  • Ching Lau
  • Elizabeth B. Claus
  • Jill Barnholtz-Sloan
  • Rose Lai
  • Dora Il’yasova
  • Joellen Schildkraut
  • Jonine L. Bernstein
  • Sara H. Olson
  • Robert B. Jenkins
  • Ping Yang
  • Amanda L. Rynerason
  • Margaret Wrensch
  • Lucie McCoy
  • John K. Wienkce
  • Bridget McCarthy
  • Faith Davis
  • Nicholas A. Vick
  • Christoffer Johansen
  • Hanne Bødtcher
  • Siegal Sadetzki
  • Revital Bar-Sade Bruchim
  • Galit Hirsh Yechezkel
  • Ulrika Andersson
  • Beatrice S. Melin
  • Melissa L. Bondy
  • Richard S. Houlston
Article

DOI: 10.1007/s10689-010-9346-5

Cite this article as:
Robertson, L.B., Armstrong, G.N., Olver, B.D. et al. Familial Cancer (2010) 9: 413. doi:10.1007/s10689-010-9346-5

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 p16INK4A/p14ARF 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 p16INK4A/p14ARF 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 p16INK4A or p14ARF. 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 p16INK4A/p14ARF and p53 mutations contribute significantly to familial glioma.

Keywords

p16INK4A/p14ARFp53MutationFamilial glioma

Supplementary material

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Lindsay B. Robertson
    • 1
  • Georgina N. Armstrong
    • 2
  • Bianca D. Olver
    • 1
  • Amy L. Lloyd
    • 1
  • Sanjay Shete
    • 2
  • Ching Lau
    • 3
  • Elizabeth B. Claus
    • 4
    • 5
  • Jill Barnholtz-Sloan
    • 6
  • Rose Lai
    • 7
  • Dora Il’yasova
    • 8
  • Joellen Schildkraut
    • 8
  • Jonine L. Bernstein
    • 9
  • Sara H. Olson
    • 9
  • Robert B. Jenkins
    • 10
  • Ping Yang
    • 10
  • Amanda L. Rynerason
    • 10
  • Margaret Wrensch
    • 11
  • Lucie McCoy
    • 11
  • John K. Wienkce
    • 11
  • Bridget McCarthy
    • 12
  • Faith Davis
    • 12
  • Nicholas A. Vick
    • 13
  • Christoffer Johansen
    • 14
  • Hanne Bødtcher
    • 14
  • Siegal Sadetzki
    • 15
  • Revital Bar-Sade Bruchim
    • 16
  • Galit Hirsh Yechezkel
    • 17
  • Ulrika Andersson
    • 18
  • Beatrice S. Melin
    • 18
  • Melissa L. Bondy
    • 2
  • Richard S. Houlston
    • 1
  1. 1.Section of Cancer GeneticsInstitute of Cancer Research (ICR)SuttonUK
  2. 2.Department of EpidemiologyM.D. Anderson Cancer Center (MDACC), The University of TexasHoustonUSA
  3. 3.Baylor College of MedicineTexas Children’s Cancer Center (TCH)HoustonUSA
  4. 4.Department of Epidemiology and Public HealthYale University School of MedicineNew HavenUSA
  5. 5.Department of NeurosurgeryBrigham and Women’s Hospital Boston (BW)BostonUSA
  6. 6.Case Comprehensive Cancer CenterCase Western Reserve University School of MedicineClevelandUSA
  7. 7.The Neurological Institute of Columbia UniversityNew YorkUSA
  8. 8.Cancer Control and Prevention Program, Department of Community and Family MedicineDuke University Medical CenterDurhamUSA
  9. 9.Department of Epidemiology and BiostatisticsMemorial Sloan-Kettering Cancer Centre (MSK)New YorkUSA
  10. 10.Mayo Comprehensive Clinic CancerMayo ClinicRochesterUSA
  11. 11.Department of Neurological SurgeryUniversity of California, San Francisco (UCSF)San FranciscoUSA
  12. 12.Division of Epidemiology and BiostatisticsUniversity of Illinois at Chicago (UIC)ChicagoUSA
  13. 13.Department of NeurologyNorthShore University HealthSystemEvanstonUSA
  14. 14.Institute of Cancer EpidemiologyDanish Cancer SocietyCopenhagenDenmark
  15. 15.Cancer and Radiation Epidemiology UnitGertner Institute, Chaim Sheba Medical CenterTel HashomerIsrael
  16. 16.Department of NeurosurgeryTel-Aviv Sourasky Medical CenterTel-AvivIsrael
  17. 17.Sackler School of MedicineTel-Aviv UniversityTel-AvivIsrael
  18. 18.Department of Radiation Sciences OncologyUmeå UniversityUmeåSweden