Genetic alterations in primary glioblastomas in Japan.

Takao Fukushima, Alexandre Favereaux, Hervé Huang, Tsuneo Shimizu, Yasuhiro Yonekawa, Yoichi Nakazato, Hiroko Ohagki
Journal of Neuropathology and Experimental Neurology. 2006-01-01; 65(1): 12-18
DOI: 10.1097/01.jnen.0000196132.66464.96

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Current knowledge of genetic alterations in glioblastomas is based largely on
genetic analyses of tumors from mainly caucasian patients in the United States
and Europe. In the present study, screening for several key genetic alterations
was performed on 77 primary (de novo) glioblastomas in Japanese patients. SSCP
followed by DNA sequencing revealed TP53 mutations in 16 of 73 (22%)
glioblastomas and PTEN mutations in 13 of 63 (21%) cases analyzed. Polymerase
chain reaction (PCR) showed EGFR amplification in 25 of 77 (32%) cases and p16
homozygous deletion in 32 of 77 (42%) cases. Quantitative microsatellite analysis
revealed LOH 10q in 41 of 59 (69%) glioblastomas. The frequencies of these
genetic alterations were similar to those reported for primary glioblastomas at
the population level in Switzerland. As previously observed for glioblastomas in
Europe, there was a positive association between EGFR amplification and p16
deletion (p=0.009), whereas there was an inverse association between TP53
mutations and p16 deletion (p=0.049) in glioblastomas in Japan. Multivariate
analyses showed that radiotherapy was significantly predictive for longer
survival of glioblastoma patients (p=0.002). SSCP followed by DNA sequencing of
the kinase domain (exons 18-21) of the EGFR gene revealed mutations in 2 ou of 69
(3%) glioblastomas in Japan and in 4 of 81 (5%) glioblastomas in Switzerland. The
allele frequencies of polymorphisms at codon 787 CAG/CAA (Gln/Gln) in
glioblastomas in Japan were G/G (82.4%), G/A (10.8%), A/A (6.8%), corresponding
to G 0.878 versus A 0.122, significantly different from those in glioblastomas in
Switzerland: G/G (27.2%), G/A (28.4%), A/A (44.4%), corresponding to G 0.414
versus A 0.586 (p < 0.0001). These results suggest that primary glioblastomas in
Japan show genetic alterations similar to those in Switzerland, suggesting a
similar molecular basis in caucasians and Asians, despite different genetic
backgrounds, including different status of a polymorphism in the EGFR gene.

DOI: 10.1097/01.jnen.0000196132.66464.96
PMID: 16410744 [Indexed for MEDLINE]

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