OBJECTIVETo evaluate whether deletion of chromosome 14q is involved in the carcinogenesis of primary glioblastoma multiforme and to identify possibly common deletion regions. METHJODS: Fourteen fluorescent dye-labeled polymorphic markers were used and polymerase chain reaction-based microsatellite analysis was employed to investigate loss of heterozygosity (LOH) on chromosome 14q in 20 primary glioblastoma multiforme (GBM).

RESULTSTen of twenty (50%) GBM displayed LOH at one or more of the markers on chromosome 14q. Five tumors showed either LOH or non-informative on all markers tested. The most frequent LOH was observed at locus D14S65 (57.1%) on 14q32.1, and in the chromosomal region spanning from D14S63 (47.1%) to D14S74 (46.7%) on 14q23-31. None of the informative loci exhibited microsatellite instability.

CONCLUSIONSAllelic deletion on chromosome 14q plays an important role in the pathogenesis of GBM. Chromosomal regions at locus D14S65 on 14q32.1 and spanning from D14S63 to D14S74 on 14q23-31 may harbor multiple tumor suppressor genes associated with GBM.

Adult ; Aged ; Chromosomes, Human, Pair 14 ; Female ; Genes, Tumor Suppressor ; Glioblastoma ; genetics ; Humans ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged

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

Adult ; Brain Neoplasms ; genetics ; DNA, Neoplasm ; analysis ; Female ; Genome ; Glioblastoma ; genetics ; Humans ; Loss of Heterozygosity ; Microsatellite Repeats ; Neoplasm Recurrence, Local ; genetics ; Polymerase Chain Reaction

OBJECTIVETo investigate molecular genetic alterations associated with primary and corresponding recurrent glioblastoma multiforme(GBM) and to identify which chromosomal regions of the whole genome may be involved in the recurrence of primary GBM.

METHODSA high-resolution allelotyping study of one patient's primary GBM and corresponding recurrent GBM was performed by PCR-based loss of heterozygosity(LOH) analysis with the use of 382 fluorescent dye-labeled polymorphic microsatellite markers covering all 22 autosomes. The mean genetic distance between two flanking markers is 10 cM.

RESULTSLOH at locus D9S157 on 9p21 and at loci D10S537, D10S185, D10S192, D10S597, D10S587, D10S217 on 10q21.3-26.3 was observed in the primary GBM. As for corresponding recurrent tumor, LOH was observed not only in expanded regions on 9p21 and 10q21.3-26.3 but also on multiple other chromosomal arms, including 1q, 7p,7q, 21q, 20p, 20q, 10p, 19p, 19q.

CONCLUSIONChromosome 9p and 10q may be involved in the development of this GBM. Although histopathological diagnoses of the primary and corresponding recurrent tumor are identical, the recurrence of GBM is characterized by an increased involvement of molecular genetic abnormalities and may be accompanied by inactivation of more tumor suppressor genes.

Adult ; Alleles ; Chromosome Mapping ; methods ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 10 ; genetics ; Chromosomes, Human, Pair 19 ; genetics ; Chromosomes, Human, Pair 20 ; genetics ; Chromosomes, Human, Pair 21 ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Chromosomes, Human, Pair 9 ; genetics ; DNA ; genetics ; Female ; Glioblastoma ; genetics ; pathology ; surgery ; Humans ; Loss of Heterozygosity ; Microsatellite Repeats ; Neoplasm Recurrence, Local

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