Chromosomal Aberrations And Their Relationship With The Resistance Of Human Lung Cancer Study

study on chromosomal aberration of human pulmonary carcinoma and its relationship withmultidrug resistanceAbstractIt has been verified that various oncogenes and inhibitory oncogenes, orienting at different sites in the chromosome, participate and lead to the occurrence and development of pulmonary carcinoma. It is helpful to analyze the rules of chromosomal aberration in pulmonary carcinoma so as to find the new related gene sites in the pulmonary carcinoma and to screen new genes. For various reasons, few systematic studies of the chromosomal aberration have been performed. In this study, we analyzed and studied the chromosomal aberration in pulmonary carcinoma and its correlation with the pathological type, multidrug resistance and clinical survival period using traditional techniques such as cytogenetics, comparative genomic hybridization(CGH) and spectral karyotyping (SKY).Results:1.Chromosoma[ aberration (shown as abnormalities of count and structure) in peripheral blood of 32% patients with pulmonary carcinoma was found. The incidence rate of chromosomal aberration was 10.7% at Stages I & II, 59.1% at the intermediate and advanced stages. There was significantly difference between the two different stages(P<0.05).2.More chromosomal aberration was found in the tissue of pulmonary carcinoma. In different types of pulmonary carcinoma, common changes were characterized by the delection of 2p, llp, l7p and 13q and the gain of 5p, lq, 8q and 5p. In non-small cell pulmonary carcinoma, changes were characterizedby the delection of 1p, 8p, 6q and 13q and the gain of 5p, 1q, 8q and 11q. Insquamous cytoma, changes were characterized by the delection of 2q36-37,and the gain of 3q and 12p, whereas adenoma was characterized by thede1ection of 9q22 and the gain of lq. In small cell pulmonary carcinoma,changes were characterized by the delection of 3p, 5q, 10q and 17p and thegain of 3q, 5p and l9p. Bat in non-specific types of carcinoma, no obviousgain of chromosome but delection of l1q was found. Compared with Gbanding, more abnormal changes in chromosome, especially the changes ofsub-banding in the sub-area, were found.3. Cell strains were constructed by the technique of large dose intervalimpact. APart from the decline of energy metabolism, other properties weresimilar tO those of the parelltal generation.4. The chromosome caryotypes of cell strains in adenocarcinoma of lungsuch as A594, A594/CDDP, SPC-A-1 and SPC-A-1/CDDP were sub-triploid.More chromosome breakages and reconstructions were found aller carcinomacel1s had been induced to drug resistance. After being comPared with theparental generation cells, the gain of 4q and 1 l q23-pter, but delection of 2p14-pter, 2q23-q23 and 7p were fOund in drug-resistance cell strain A549/CDDP.The gain of 6q, l1q23-qter and the delection of 2pl4-pter, 2q23-q24 and 7qwere fOund in cell SPC-A-l/CDDP5. Chromosome translocation of several chromosomes was found usingspectral karyotyping (SKY). Several unknown chromosomes when ana1yzed byG banding, being derivative reconstructed chromosomes after the chromosomebreakage, were verified. After being compared with the parenta1 generationcells, several derivative chromosomes in the two drug-resistance cel1 strainsand an identicaI chromosome der(2l)t(2l;22) were fOund.6. The analysis of the chromosome cu1tured by using the lymphocytes ofperipheral blood of patients after operation with high survival fate showed thatIVthe incidence rate of chromosomal aberration was 3.27%, which wassignifican1y lower than l0.85% of patients without operation(P<0.0001).7. Of the 15 cases of high survival rate, chromosoma1 aberration was fOundin l l cases, not in 4 cases, but the involved number of chromosomes was smalJ.Of the tWo or more cases that changed on the same spot, chromosomes werecharacterized by the gain of 3q and 1q and delection of 2q in squamouscarcinoma; the gain of lq and delection of 9q in adenocarcinoma; the ga...