Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation.
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.
Robertson
Lindsay B
LB
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
Armstrong
Georgina N
GN
Olver
Bianca D
BD
Lloyd
Amy L
AL
Shete
Sanjay
S
Lau
Ching
C
Claus
Elizabeth B
EB
Barnholtz-Sloan
Jill
J
Lai
Rose
R
Il'yasova
Dora
D
Schildkraut
Joellen
J
Bernstein
Jonine L
JL
Olson
Sara H
SH
Jenkins
Robert B
RB
Yang
Ping
P
Rynearson
Amanda Lynn
AL
Rynerason
Amanda L
AL
Wrensch
Margaret
M
McCoy
Lucie
L
Wienkce
John K
JK
McCarthy
Bridget
B
Davis
Faith
F
Vick
Nicholas A
NA
Johansen
Christoffer
C
Bødtcher
Hanne
H
Sadetzki
Siegal
S
Bruchim
Revital Bar-Sade
RB
Yechezkel
Galit Hirsh
GH
Andersson
Ulrika
U
Melin
Beatrice S
BS
Bondy
Melissa L
ML
Houlston
Richard S
RS
D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D019942:Genes, p16; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D055815:Young Adult
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