Familial Cancer

, Volume 9, Issue 3, pp 413–421 | Cite as

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

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 

Notes

Acknowledgments

We are grateful to all patients, their clinicians and other individuals for their participation in this study. Work was undertaken with grant support from NIH R01 CA119215 01, American Brain Tumor Association, and National Brain Tumor Society and the Tug McGraw Foundation. Work in the Houlston laboratory is supported by Cancer Research UK (Bobby Moore C1298/A8362).

We acknowledge the following Gliogene Consortium members; Phyllis Adatto, Fabian Morice (MADCC); Lisa Calvocoressi, Kate Saunders (BW); Karen Devine, Gene Barnett, Cathy Brewer, Elizabeth Ennis (Case); Stacy Murray (Duke); Mitchel Berger, Susan Chang, Michael Prados, Terri Rice (UCSF); Christina Corpuz, Erika Florendo, Steven Rosenfeld (Columbia University); Candice Zahora (UIC); Jan C Buckner, Caterina Giannini, Brian P O’Neill, Deb Sprau (Mayo Clinic); Lisa M. DeAngelis, Erica Schubert, Sharon Bayuga (MSK); Pat Lada (NorthShore University HealthSystem); Deborah T. Blumenthal (Gertner Institute); Zvi Ram (Tel-Aviv University); Hans Bolander, Gudrun Byström, Roger Henriksson, Guiseppe Stragliotti and Fredrik Wiklund (Umeå University).

Supplementary material

10689_2010_9346_MOESM1_ESM.doc (44 kb)
(DOC 44 kb)

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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

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