Published in:
01-09-2010
Survey of familial glioma and role of germline p16
INK4A
/p14
ARF
and p53 mutation
Authors:
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
Published in:
Familial Cancer
|
Issue 3/2010
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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.