A novel low-penetrance locus for familial glioma at 15q23-q26.3

Epidemiological studies and case reports suggest that familial clustering of gliomas may occur in families that do not fit any known tumor syndromes. In the present study, 15 familial glioma pedigrees from a limited geographical area were hypothesized to carry the same low-penetrance susceptibility...

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Published inCancer research (Chicago, Ill.) Vol. 62; no. 13; pp. 3798 - 3802
Main Authors PAUNU, Niina, LAHERMO, Päivi, ONKAMO, Päivi, OLLIKAINEN, Vesa, RANTALA, Immo, HELEN, Pauli, SIMOLA, Kalle O. J, KERE, Juha, HAAPASALO, Hannu
Format Journal Article
LanguageEnglish
Published Philadelphia, PA American Association for Cancer Research 01.07.2002
Subjects
Biological and medical sciences
Brain Neoplasms - genetics
Chromosome Mapping
Chromosomes, Human, Pair 15
Female
Genetic Predisposition to Disease - genetics
Genome, Human
Glioma - genetics
Haplotypes
Humans
Linkage Disequilibrium
Male
Medical sciences
Medicin och hälsovetenskap
Neurology
Pedigree
Penetrance
Tumors of the nervous system. Phacomatoses
Human
Nervous system diseases
Linkage
Long arm
Family study
Biological marker
Genotype
Malignant tumor
Malignant glioma
Allele
Chromosome D15
DNA
Gene penetrance
Central nervous system disease
Molecular epidemiology
Genetics
Familial cancer
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Summary:Epidemiological studies and case reports suggest that familial clustering of gliomas may occur in families that do not fit any known tumor syndromes. In the present study, 15 familial glioma pedigrees from a limited geographical area were hypothesized to carry the same low-penetrance susceptibility allele. We used a two-stage strategy for disease gene mapping. A genome scan in four glioma families revealed four interesting loci at chromosome arms 1q, 6q, 8p, and 15q. Additional markers in these regions provided evidence of significant linkage to 15q23-q26.3 with a maximum nonparametric linkage score of 3.35 with marker D15S130. Investigation of all 15 glioma families by association analysis (haplotype pattern mining) and through use of the transmission/disequilibrium test gave further evidence of significant association/transmission distortion at the same 15q locus (P = 0.02 and P = 0.03, respectively). No evidence of involvement of known tumor syndromes was obtained from the data provided by the linkage analysis or hospital records. Thus, the first genome-wide linkage analysis of familial glioma suggests a novel susceptibility locus at 15q23-q26.3.
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ISSN:0008-5472
1538-7445