title: Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation.
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.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: Robertson
authors.forename: Georgina N
authors.initials: GN
authors.lastname: Armstrong
authors.forename: Bianca D
authors.initials: BD
authors.lastname: Olver
authors.forename: Amy L
authors.initials: AL
authors.lastname: Lloyd
authors.forename: Sanjay
authors.initials: S
authors.lastname: Shete
authors.forename: Ching
authors.initials: C
authors.lastname: Lau
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Claus
authors.forename: Jill
authors.initials: J
authors.lastname: Barnholtz-Sloan
authors.forename: Rose
authors.initials: R
authors.lastname: Lai
authors.forename: Dora
authors.initials: D
authors.lastname: Il'yasova
authors.forename: Joellen
authors.initials: J
authors.lastname: Schildkraut
authors.forename: Jonine L
authors.initials: JL
authors.lastname: Bernstein
authors.forename: Sara H
authors.initials: SH
authors.lastname: Olson
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Amanda Lynn
authors.initials: AL
authors.lastname: Rynearson
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Rynerason
authors.forename: Margaret
authors.initials: M
authors.lastname: Wrensch
authors.forename: Lucie
authors.initials: L
authors.lastname: McCoy
authors.forename: John K
authors.initials: JK
authors.lastname: Wienkce
authors.forename: Bridget
authors.initials: B
authors.lastname: McCarthy
authors.forename: Faith
authors.initials: F
authors.lastname: Davis
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Vick
authors.forename: Christoffer
authors.initials: C
authors.lastname: Johansen
authors.forename: Hanne
authors.initials: H
authors.lastname: Bødtcher
authors.forename: Siegal
authors.initials: S
authors.lastname: Sadetzki
authors.forename: Revital Bar-Sade
authors.initials: RB
authors.lastname: Bruchim
authors.forename: Galit Hirsh
authors.initials: GH
authors.lastname: Yechezkel
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.forename: Beatrice S
authors.initials: BS
authors.lastname: Melin
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Bondy
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: 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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