Purpose:20 loci on chromosome 6 were examined to detect loss of heterozygosity(LOH)in 21 cases of glioblastoma(GBM) in order to locate the deletion areas probably harboring tumor suppressor genes.Methods:PCR based microsatellite polymorphism analyses were performed to detect LOH on chromosome 6, fluorescence labeled primers and Perkin Elmer 377 DNA Sequencer were applied.Results:47.6% informative cases of GBM displayed LOH on chromosome 6, 28.1% of informative loci showed LOH in our series, in which the most frequent LOH were observed at locus D6S281 (50%) on 6q tel and D6S287(50%) on 6q 16.3 ,the LOH frequency at locus D6S276 on 6p 21.1 21.3 is also high(35.3%).Conclusions:Loss of genetic material on chromosome 6 may be involved in the molecular genetic pathogenesis of GBM. The chromosomal regions at loci D6S281 on 6q tel ,D6S287 on 6q 16.3 and D6S276 on 6p 21.1 21.3 may harbor tumor suppressor genes associated with GBM. [

OBJECTIVETo reveal the molecular genetic mechanisms for the pathogenesis of glioblastoma (GBM) and determine which chromosomes or chromosomal regions may play a role in the pathogenesis of GBM or may harbor tumor suppressor genes (TSGs) associated GBM.

METHODSAn allelotype study of 21 cases of GBM was performed by polymerase chain reaction and loss of heterozygosity (LOH) analysis. Three hundred and eighty-two microsatellite markers covering all 22 autosomes were used. The mean genetic distance between two flanking markers is about 10 cM. Fluorescent dye-labeled primers and Perkin Elmer 377 DNA Sequencer were applied.

RESULTSLOH was observed on all chromosomal arms examined in this study. The LOH frequencies of 10q, 10p, 13q, 17p and 9p were the highest (>50%), on which high LOH frequencies were detected at the regions resided by the known TSGs including PTEN, DMBT1, p16, p15, p53 and Rb. The following commonly deleted regions were detected: 9p22-23, 10p12.2-14, 10q21.3, 13q12.1-14.1, 13q14.3-31, 17p11.2-12, 17p13, 3q24-27, 11p12-13, 14q31-32.3, 14q21-24.1, 22q13.2-13.3, 4q35, 4q31.1-31.2, 6qtel, 6q16.3.

CONCLUSIONThis study demonstrated that the pathogenesis of GBM is very complicated and associated with various molecular genetic abnormalities on lots of chromosomes. The chromosomal arms most closely relevant to the pathogenesis of GBM are 10q, 10p, 9p, 17p and 13q. Besides the well-known TSGs, such as PTEN, DMBT1, p16, p15, p53 and Rb, multiple unknown TSGs associated with GBM may be present on the commonly deleted regions observed for the first time in this study.

Adult ; Aged ; Chromosomes, Human ; genetics ; DNA, Neoplasm ; genetics ; Female ; Glioblastoma ; genetics ; Humans ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged

OBJECTIVETo investigate the molecular genetic pathogenesis of primary glioblastoma multiforme (GBM) and identify which chromosomes or chromosomal regions of the entire genome may harbor tumor suppressor genes (TSGs) associated with GBM.

METHODSA high-resolution allelotype study of 21 cases of primary GBM was performed by PCR-based loss of heterozygosity (LOH) analysis. Three hundred and eighty-two fluorescent dye-labeled microsatellite markers covering all 22 autosomes were applied. The mean genetic distance between two flanking markers was about 10 cM.

RESULTSLOH was observed on all 39 nonacrocentric autosomal arms examined in this study. The LOH frequencies of 10q, 10p, 9p, 17p and 13q were the highest (> 50%). Furthermore, high LOH frequencies were detected in the regions containing known TSGs including PTEN, DMBT1, p16, p15, p53 and RB; the LOH frequencies on 14q, 3q, 22q, 11p, 9q, 19q were also high (> 40.5%). Our study observed the following commonly deleted regions: 9p22-23, 10p12.2-14, 10q21.3, 13q12.1-14.1, 13q14.3-31, 17p11.2-12, 17p13, 3q25.2-26.2, 11p12-13, 14q13-31, 14q32.1, 14q11.1-13, 22q13.3, 4q35, 4q31.1-31.2, 6q27 and 6q21-23.3.

CONCLUSIONSThe molecular pathogenesis of GBM is very complicated and associated with a variety of genetic abnormalities on many chromosomal arms. The most closely related chromosomal arms to the pathogenesis of GBM are 10q, 10p, 9p, 17p and 13q. Besides the well-known TSGs including PTEN, DMBT1, p16, p15, p53 and RB, multiple unknown TSGs associated with GBM may be present on the commonly deleted regions detected in the present study.

Adult ; Aged ; Alleles ; Chromosome Aberrations ; DNA ; isolation & purification ; Female ; Genome ; Glioblastoma ; genetics ; Humans ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged ; Polymerase Chain Reaction