Genetic Alterations in Primary Glioblastomas in Japan

ABSTRACTCurrent 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...

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Published in:	Journal of neuropathology and experimental neurology Vol. 65; no. 1; pp. 12 - 18
Main Authors:	Fukushima, Takao, Favereaux, Alexandre, Huang, Hervé, Shimizu, Tsuneo, Yonekawa, Yasuhiro, Nakazato, Yoichi, Ohagki, Hiroko
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD American Association of Neuropathologists, Inc 01-01-2006 Lippincott Williams & Wilkins Oxford University Press
Subjects:	Adult Aged Aged, 80 and over Antineoplastic agents Biological and medical sciences Chemotherapy Chi-Square Distribution Chromosomes, Human, Pair 10 Cyclin-Dependent Kinase Inhibitor p16 - genetics ErbB Receptors - genetics Female Follow-Up Studies Glioblastoma - epidemiology Glioblastoma - genetics Humans Japan - epidemiology Loss of Heterozygosity - genetics Male Medical sciences Middle Aged Multivariate Analysis Mutation - genetics Neurology Pharmacology. Drug treatments PTEN Phosphohydrolase - genetics Retrospective Studies Reverse Transcriptase Polymerase Chain Reaction - methods Sequence Analysis, DNA - methods Survival Rate Switzerland - epidemiology Tumor Suppressor Protein p53 - genetics Tumors of the nervous system. Phacomatoses Asia Japan Nervous system diseases Glioblastoma Alteration Malignant tumor TP53 mutation EGFR mutation Malignant glioma Central nervous system disease Deletion Genetics LOH 10q Mutation PTEN mutation p16INK4a deletion EGFR amplification
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Summary:	ABSTRACTCurrent 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 SwitzerlandG/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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3069 1554-6578
DOI:	10.1097/01.jnen.0000196132.66464.96