Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas.
BACKGROUND
Deletions of 19q have been associated with gliomas, especially oligodendrogliomas. In addition, cases with oligodendrogliomas with the 19q deletion have been observed to have a better survival compared with cases without the 19q deletion. The authors have previously described a 150-kilobase minimal deletion region in gliomas that maps to 19q13.33 and contains 3 novel candidate genes (GLTSCR1, EHD2, and GLTSCR2).


METHODS
The authors performed an association study using 141 cases with gliomas (61 cases with astrocytomas, 40 cases with oligodendrogliomas, 40 cases with mixed oligoastrocytomas) and 108 general controls. They evaluated 7 single nucleotide polymorphisms (SNPs) in 6 genes within and nearby the minimal 19q deletion region (ERCC2, RAI, ASE-1, ERCC1, GLTSCR1, and LIG1).


RESULTS
The prevalence of a germline GLTSCR1-exon-1 T allele (SNP rs1035938) was 40% in cases with oligodendrogliomas compared with 27% in controls (P = 0.029), and the prevalence of an ERCC2-exon-22 T allele (SNP rs1052555) was 35% in cases with oligodendrogliomas compared with 18% in controls (P = 0.043). One high-risk and 1 low-risk haplotype were associated with oligodendroglioma development (P = 0.003 and 0.026, respectively). Cases with oligodendrogliomas with the 19q deletion had a significantly higher frequency of the GLTSCR1-exon-1 T allele compared with cases without the 19q deletion (P = 0.01). It was noteworthy that cases with gliomas who were homozygous for the GLTSCR1-exon-1 T allele had a significantly better survival: 77% and 68% survival at 2 and 5 years compared with 56% and 34% for other genotypes (P = 0.02, log-rank test). Multivariable analysis identified grade, age, and the GLTSCR1-exon-1 and ERCC2-exon-22 genotypes as independent predictors for survival.


CONCLUSIONS
These results suggested that alterations in GLTSCR1 (or a closely linked gene) were associated with the development and progression of oligodendroglioma.
Yang
Ping
P
Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. yang.ping@mayo.edu
Kollmeyer
Thomas M
TM
Buckner
Kristin
K
Bamlet
William
W
Ballman
Karla V
KV
Jenkins
Robert B
RB
D001254:Astrocytoma / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002872:Chromosome Deletion; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein
D004268:DNA-Binding Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human