aphidicolin and Carcinoma--Non-Small-Cell-Lung

Fragile sites are nonrandomly located gaps and/or breaks and their expres-sion can be induced by specific culture conditions. There are many reports in the literature that indicate that these sites can act as factors that predispose to specific chromosome aberrations and other complex rearrangement in the chromosome and their association with cancers. In the present study, the expression of the fragile sites induced by aphidicolin was evaluated on prometaphase chromosomes from peripheral blood lymphocytes of 55 patients with breast cancer patients belonging to different stages of the cancer, 25 patients with epithelial ovarian cancer, and 13 with non-small-cell lung cancer, 100 of their first-degree clinically healthy female relatives, and 100 normal age-matched healthy persons without a familial history of cancer. The frequency of expression of the fragile sites in cancer patients and their first-degree relatives was found to be statistically significant (P<0.05) than those of the controls. In different stages of breast cancer patients, 6q26 is the best-defined fragile site whereas 13q13 is confined to stage II and stage III patients only. The chromosomal aberration rate/cell in breast cancer patients was found to be 0.29+/-0.13, in epithelial ovarian cancer patients 0.38+/-0.14, and in non-small-cell lung cancer 0.29+/-0.11 as compared to 0.07+/-0.03 in controls, and was found to be statistically significant. Therefore, our results indicate that these fragile sites may be the unstable sites in the genome and, hence, can be used as suitable and reliable markers for genetic predisposition to breast cancer, epithelial ovarian cancer, and in non-small-cell lung cancer.

Topics: Aphidicolin; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Chromosome Fragile Sites; Chromosome Fragility; Chromosome Mapping; Female; Genetic Predisposition to Disease; Humans; Lung Neoplasms; Lymphocytes; Neoplasm Staging; Ovarian Neoplasms

Fragile sites are non-staining gaps and breaks in specific points of chromosomes that are inducible by various culture conditions. Previous studies have shown that various clastogenic agents increase expression of fragile sites. In this study, the expression of common fragile sites induced by aphidicolin was evaluated on prometaphase chromosomes obtained from peripheral blood lymphocytes. Chromosomal aberrations and fragile site expression of 60 individuals, including 20 patients with non-small cell lung cancer (NSCLC), 20 of their clinically healthy family members, and 20 age-matched normal healthy controls without history of any cancer type were studied. Both the proportion of damaged cells (P < 0.001) and the mean number of gaps and breaks per cell (P < 0.001) were significantly higher in both the patients and relatives' groups when compared with the control group. However, they were insignificant when the patients were compared to their relatives (P > 0.05). We determined four aphidicolin type common fragile sites in our study. These sites in patients with NSCLC and relatives were the following: 1p21, 2q33, 3p14, and 16q23. In these fragile sites, 2q33, 3p14, and 16q23 sites were statistically significant when compared with control group (P < 0.001, P < 0.0005, and P < 0.05, respectively). Consequently, we believe that fragile site studies may be helpful to detection of cancer risk.

Topics: Adolescent; Adult; Aged; Aphidicolin; Carcinoma, Non-Small-Cell Lung; Child; Chromosome Aberrations; Chromosome Fragile Sites; Chromosome Fragility; Chromosome Mapping; Family Health; Female; Genetic Predisposition to Disease; Humans; Lung Neoplasms; Male; Middle Aged; Models, Genetic; Models, Statistical; Mutation; Smoking