Chromosomal Abnormality Analysis Of Lung Carcinoma By Comparative Genomic Hybridization And Multicolour Fluorescent In Situ Hybridization

Objective: To identify chromosomal abnormality in lung cancer by the molecular cytogenetic techniques of comparative genomic hybridisation (CGH) and multicolour fluorescent in situ hybridization (M-FISH) and to comprehend the relationship between chromosome abnormality, different patho-types, and clinical features of lung cancer.Methods: There were two parts in this study. In the first part, CGH was used to detect the global genomic aberration in the fresh cancer tissue cells of 30 patients with lung cancer. In the second part, R banding karyotype analysis, CGH and M-FISH were simultaneously used to analyze chromosomal abnormalities in tissue cells of one primary small-cell lung cancer (SCLC) and two lung cancer cell lines, which evlluated the relationship between chromosomal gain or lose and interchromosomal unbalanced translocation.Result: 1. Chromosomal abnormality were detected in all of 30 cases with lung cancer, and each case was involved in at least two chromosomes. There were no significant differences between different patho-types of lung cancer. The incidence of chromosomal gains were higher than that of losses, the rate was 2∶1 .2. The altofrequent gains in 1p11-p22, 5p11-p14, 16p11-P12, 19q13, 19p13, 20p12, 21q21 and the altofrequent loses in 5q, 6p24-pter, 9p31-qter, 13q21-qter, 14q21-qter were found in all three types of lung cance[SCLC, adenocarcinoma(AC) and squamous cell carcinoma(SCC)].3. The marked differences of chromosomal abnormalities in three types of lung cancer were also found: (1) In SCLC, the frequencies of gain in 6p12-p21 and 4p13-p15 (70% and 50% respectively) were significantly higher than those in SCC and AC(P<0.05, =0.05), the frequencies of gain in 11p11-p14 and 18q12 (70% and 60% respectively) were significantly higher than those in AC(P<0.05, <0.05), the frequency of gain in 18p11 (50%) was significantly higher than that in SCC(P=0.05), the frequencies of losses in 8q22-qter and 4q (50% and 50% respectively) were significantly higher than those in SCC(P<0.05, =0.05). (2) In SCC, the frequency of gain in 2p12-p16 (40%) was significantly higher than that in AC(P<0.05), the frequency of gain in 3q24-qter (40%) was significantly higher than that in SCLC(P<0.05). (3) In AC, the frequencies of losses in 2p and 8q22-qter(50% and 50% respectively) were significantly higher than those in SCC(P<0.05, <0.05).4. Four and two chromosomal abnormalities were found by R banding in cell line A-549 and H-1299 respectively, and the major abnormalities were big fragment deletion, derivation or insertion. Chromosomes of primary SCLC were quiter short and small and couldn't be analyzed by R banding. Seven, six, and sixteen abnormal chromosomes were found by CGH in cell line A-549, H-1299, and primary SCLC respectively, and the major aberrations were gains or losses. Seven, eight, and thirteen chromosomal abnormalities were found by M-FISH in cell line A-549, H-1299, and primary SCLC respectively, and the major abnormalities were interchromosomal unbalanced translocations.5. In the primary SCLC, the frequencies of interchromosomal unbalanced translocations in eight chromosomes (1, 5, 7, 8, 9, 16, 18 and 19) were particularly high, and the frequent translocations were t(9;14), t(16;19), t(16;17), t(2;5;18) and t(7;12;19).6. M-FISH found some unbalanced translocation in the abnomal chromosomes (with derivations, gains or loses) detected by R banding and CGH in cell line A-549, H-1299, and primary SCLC.Conclusion:1. The cytogenetic aberration exists generally in lung cancer cells, chromosomal gains are more common than losses in lung cancer cells. The cytogenetic aberration is the base of the initiation and progression of the lung cancer.2. There are some common chromosomal abnormalities in different types of lung cancers(SCLC, SCC and AC). However, there are some different chromosomal abnormalities between SCLC, AC and SCC, which may result in the different biological behaviors of the three types of lung cancer, and may serve as a marker to antidiastole three types of lung cancer.3. As to the progression of malignant neoplastic disease, the complexity of chromosomal abnormality is obviously elevated.4. Different carcinogenic agents(smoking for example) may induce different chromosomal abnormalities.5. Karyotype analysis, CGH, and M-FISH have fortes and shortages respectively. M-FISH in combination with Karyotype analysis and CGH has enabled the highly complex chromosomal abnormalities of lung cancer to be analysed in far greater detail.6. Chromosomal abnormalities are more complex in primary lung cancer than those in cell lines. The use of analysing analyse the chromosomal abnormalities in primary lung cancer will really reveal the effect of chromosomal abnormalities on the initiation and progression of the lung cancer.