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

• Published in: Familial cancer 2010-09, Vol.9 (3), p.413-421
• Main Authors: Robertson, Lindsay B., Armstrong, Georgina N., Olver, Bianca D., Lloyd, Amy L., Shete, Sanjay, Lau, Ching, Claus, Elizabeth B., Barnholtz-Sloan, Jill, Lai, Rose, Il’yasova, Dora, Schildkraut, Joellen, Bernstein, Jonine L., Olson, Sara H., Jenkins, Robert B., Yang, Ping, Rynerason, Amanda L., Wrensch, Margaret, McCoy, Lucie, Wienkce, John K., McCarthy, Bridget, Davis, Faith, Vick, Nicholas A., Johansen, Christoffer, Bødtcher, Hanne, Sadetzki, Siegal, Bruchim, Revital Bar-Sade, Yechezkel, Galit Hirsh, Andersson, Ulrika, Melin, Beatrice S., Bondy, Melissa L., Houlston, Richard S.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biomedical and Life Sciences; Biomedicine; Brain Neoplasms - genetics; Cancer Research; Child; Child, Preschool; DNA Mutational Analysis; Epidemiology; familial glioma; Female; Genes, p16; Genes, p53; Genetic Predisposition to Disease; Germ-Line Mutation; Glioma - genetics; Human Genetics; Humans; Male; Middle Aged; mutation; p16INK4A/p14ARF; p53; Pedigree; Polymerase Chain Reaction; Young Adult
• ISSN: 1389-9600; 1573-7292; 1573-7292
• DOI: 10.1007/s10689-010-9346-5

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.