Objective: To investigate the association between three single nucleotide polymorphisms-2562G＞A,-416C＞G and-232G＞A in Tim-3(T cell immunoglobulin domain and mucin domain protein 3)gene promoter region and child allergic asthma in Chinese Han population by using family-based association study.Methods: Genotypes of 3 SNPs(-2562G＞A,-416C＞G and-232G＞A)in 118 allergic asthma nuclear pedigrees were analyzed by restriction fragment length polymorphism.The genotype data were analyzed by using the family-based transmission disequilibrium test(TDT).Haplotypes and their frequencies were established and analyzed by TRANSMIT software.Results: ①No transmission disequilibrium was found at the-2562G＞A and-232G＞A sites from heterozygous parents onto patients in 118 trios analyzed by TDT(P＞0.05);However,at the-416 C＞G locus,the observed values of G allele from heterozygous parents to offspring were significantly higher than the expected values(P＜0.05)②The haplotype TDT analysis by TRANSMIT showed the observed and the expected value in GCA and GGA haplotype from parents to the affected offsprings had significant difference respectively(P＜0.05).The Global X~2 test results also showed that Tim-1 haplotype were associated with child allergic asthma(X~2 = 17.26, P＜0.01).Conclusion: Tim-1 gene promoter-416C＞G locus are associated with allergic asthma susceptibility in Hubei Chinese Han population and the haplotypes constructed by-416C＞G are also associated with asthma.Tim-1 genetic polymorphism may play an important role in the pathogenesis of asthma.

OBJECTIVETo explore the molecular genesis of medulloblastomas with cDNA array.

METHODSFour samples of medulloblastomas and 1 sample of normal brain tissue were collected freshly. After total RNA extraction, the (32)P targeted cDNA probes were converted and then hybridized with Atlas Human Cancer Array 1.2. The gene expression profiles were acquired through autoradiography. The discrepancy between the tumor and the normal brain tissue was analyzed with Atlas Image 1.01a.

RESULTSIn comparison with the genes in the normal brain tissue, 6 down-regulated and 35 up-regulated genes in the medulloblastomas were revealed by means of the microarrays and autoradiography, and were verified by reverse transcriptase-PCR. The regulatory trends of most differential expression genes were in compliance with the biological features of this tumor.

CONCLUSIONMedulloblastomas are diseases involving multiple genes with some molecular pathological mechanisms different from the astrocytic gliomas. There are complex interrelationships between these genes, which need to be further researched.

Child ; Child, Preschool ; Gene Expression Profiling ; Humans ; Medulloblastoma ; genetics ; Oligonucleotide Array Sequence Analysis

OBJECTIVETo investigate the differential gene expression of ependymomas.

METHODSFour fresh samples of ependymomas and 1 of normal brain tissue were collected during operation. The extracted total RNAs were converted as (32)P tagged cDNA probes, which were then hybridized with the Atlas Human Cancer Array, producing the array based hybridization maps following the protocol provided with the kit. A set of special software was applied to the analysis and RT-PCR was performed to test the result.

RESULTIn comparison with the normal brain tissue, there were 31 upregulated gene and 1 downregulated gene in ependymomas, most of which were firstly found to be differentially expressed in this kind of tumor.

CONCLUSIONThe discrepancy of gene expression profiles between ependymomas and normal brain tissues is highly put through and effectively detected with cDNA array, which provides new information for the further research on the molecular mechanisms of this lesion.

Brain ; metabolism ; Brain Neoplasms ; genetics ; Ependymoma ; genetics ; Gene Expression Profiling ; Humans ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo characterize the profile of chromosomal imbalances of rhabdomyosarcoma(RMS).

METHODSComparative genomic hybridization (CGH) was used to investigate genomic imbalances in 25 cases of primary RMS including 10 cases of alveolar rhabdomyosarcoma (ARM), 12 cases of embryonic rhabdomyosarcoma (ERMS), 3 cases of polymorphic rhabdomyosarcoma (PRMS) and 2 RMS cell lines (A240 originated from ARMS and RD from PRMS), with correlation to histological type, pathologic grading, clinical staging, gender and age, respectively.

RESULTSAll twenty-five rhabdomyosarcomas showed evidence of increased or decreased DNA sequence copy numbers involving one or more regions of the genome. (1) The frequently gained chromosome regions in RMS were 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q, 18q, and the frequently lost chromosome regions were 3p, 11p, 6p. (2) The frequently gained chromosome arms in ARMS were 12q, 2p, 6, 2q, 4q, 10q, 15q. The frequently lost chromosome arms were 3p, 6p, 1q, 5q. The frequently gained chromosome regions in ERMS were 7p, 9q, 2p, 18q, 1p, 8q. The frequently lost chromosome arms in ERMS were 11p. (3) The frequently gained chromosome arms in translocation associated RMS were 12q, 2, 6, 10q, 4q and 15q (> 30%), 3p, 6p, 5q (> 30%) were the frequently loss chromosome arms. The frequently gained chromosome regions in non-translocation associated RMS were 2p, 9q, 18q (> 30%), and 11p, 14q (> 30%) were the frequently loss chromosome regions. Gain of 12q was significantly correlated with the translocation-associated tumors (P < 0.05). (4) Gains of 9q was significantly correlated with clinical staging (P < 0.05).

CONCLUSIONSGain of 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q, 18q and loss of 3p, 11p, 6p may be involved in the tumorigenesis of RMS. Gains of 12q may be correlated with gene fusion/chromosomal translocation in ARMS. Gains of 9q may be correlated with an early tumor stage of RMS.

Adolescent ; Adult ; Aged ; Carcinoma, Squamous Cell ; genetics ; Child ; Child, Preschool ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes ; Comparative Genomic Hybridization ; methods ; Female ; Gene Fusion ; Humans ; Infant ; Male ; Middle Aged ; Neoplasm Staging ; Rhabdomyosarcoma ; genetics ; Spectral Karyotyping ; methods ; Young Adult

AIDS-Related Opportunistic Infections ; diagnostic imaging ; drug therapy ; etiology ; Adult ; Bone Marrow Examination ; CD4 Lymphocyte Count ; Female ; Humans ; Male ; Middle Aged ; Mycoses ; diagnostic imaging ; drug therapy ; etiology ; Penicillium ; isolation & purification ; Prognosis ; Radiography

BACKGROUNDPrevious cytogenetic studies revealed aberrations varied among the three subtypes of rhabdomyosarcoma. We profiled chromosomal imbalances in the different subtypes and investigated the relationships between clinical parameters and genomic aberrations.

METHODSComparative genomic hybridization was used to investigate genomic imbalances in 25 cases of primary rhabdomyosarcomas and two rhabdomyosarcoma cell lines. Specimens were reviewed to determine histological type, pathological grading and clinical staging.

RESULTSChanges involving one or more regions of the genome were seen in all rhabdomyosarcomal patients. For rhabdomyosarcoma, DNA sequence gains were most frequently (> 30%) seen in chromosomes 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q and 18q; losses from 3p, 11p and 6p. In aggressive alveolar rhabdomyosarcoma, frequent gains were seen on chromosomes 12q, 2p, 6p, 2q, 4q, 10q and 15q; losses from 3p, 6p, 1q and 5q. For embryonic rhabdomyosarcoma, frequent gains were on 7p, 9q, 2p, 18q, 1p and 8q; losses only from 11p. Frequently gained chromosome arms of translocation associated with rhabdomyosarcoma were 12q, 2, 6, 10q, 4q and 15q; losses from 3p, 6p and 5q. The frequently gained chromosome arms of nontranslocation associated with rhabdomyosarcoma were 2p, 9q and 18q, while 11p and 14q were the frequently lost chromosome arms. Gains on chromosome 12q were significantly correlated with translocation type. Gains on chromosome 9q were significantly correlated with clinical staging.

CONCLUSIONSGains on chromosomes 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q and 18q and losses on chromosomes 3p, 11p and 6p may be related to rhabdomyosarcomal carcinogenesis. Furthermore, gains on chromosome 12q may be correlated with translocation and gains on chromosome 9q with the early stages of rhabdomyosarcoma.

Cell Line, Tumor ; Chromosome Aberrations ; Chromosomes, Human, Pair 12 ; genetics ; Comparative Genomic Hybridization ; methods ; Gene Fusion ; genetics ; Humans ; Oncogene Proteins, Fusion ; genetics ; Rhabdomyosarcoma ; genetics ; Tumor Cells, Cultured