BACKGROUND: Tumors are usually considered to be clonal progeny of single transformed cells. Carcinosarcomas and malignant mixed epithelial tumors are examples where controversies exist regarding the singularity or multiplicity of their cell of origin. METHODS: The authors examined the clonality of carcinosarcomas (7 cases) and malignant mixed epithelial tumor (5 cases) in female patients by X-chromosome inactivation as a marker. Each component of the tumors were picked up by the laser capture microscope. The polymorphic exon 1 CAG trinucleotide repeat in the X-linked human androgen receptor (HUMARA) gene was amplified by a polymerase chain reaction before and after treatment of the methylation-sensitive endonuclease HpaII. RESULTS: Eleven cases were informative for clonality determination. Six out of seven carcinosarcomas and three out of four malignant mixed epithelial tumors revealed the same patterns of X-chromosome inactivation, which suggests that they are monoclonal. In contrast, the patterns of X-chromosome inactivation were different between the two tumor components in each cases of carcinosarcoma and malignant mixed epithelial tumor, indicating that they are of polyclonal origin. CONCLUSIONS: These observations show that although most of carcinosarcomas and malignant mixed epithelial tumors are of monoclonal origin, some of them are of polyclonal origin. This finding suggests that these tumors are genuinely polyclonal, and that they originated in the neoplastic transformation of more than one somatic cells
Carcinosarcoma* ; Deoxyribonuclease HpaII ; Exons ; Female ; Humans ; Polymerase Chain Reaction ; Receptors, Androgen ; Trinucleotide Repeats

OBJECTIVETo study the clonality of uterine leiomyomas, especially the relationship between different nodules in multinodular cases.

METHODSGenomic DNA was extracted from fresh tissue samples and digested through incubation with Hpa II and amplified through nested polymerase chain reaction for phosphoglycerate kinase (PGK) gene. The products were treated with Bst XI and resolved on agarose gels.

RESULTSAmong the 103 cases examined, 32 (31%) carried the polymorphic Bst XI site at the PGK locus. Eighty-nine tumors from the 29 cases were subjected to the cloning assay. Loss of polymorphism at the PGK locus was found in all tumor nodules, indicating the monoclonality of the tumor. The relationship between multiple tumors was also assessed by comparing their inactivated alleles. Seven nodules from a leiomyosarcoma were found to have originated from a single cell. However, the relationship was found to be more complicated, as demonstrated in 15 cases of multiple leiomyomas. The same inactivated allele was found in all nodules of 8 cases and in most nodules in 2 cases, while totally different inactivation patterns were observed in 5 cases. The difference was not associated with cell proliferation.

CONCLUSIONSClonality analysis can be applied to define the clonality of focal or nodular lesions. Uterine leiomyomas are of clonal origin. Multiple uterine leiomyomas may be subtyped into fully independent and aggressive types as well as a mixed type of both.

Base Sequence ; Clone Cells ; DNA, Neoplasm ; genetics ; metabolism ; Deoxyribonuclease HpaII ; metabolism ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Female ; Humans ; Leiomyoma ; genetics ; pathology ; Neoplasms, Multiple Primary ; genetics ; pathology ; Uterine Neoplasms ; genetics ; pathology

OBJECTIVETo study the polymorphism of CYP1A1 gene Msp I site in the Mongolian and Han nationality populations of Inner Mongolia.

METHODSThe PCR-restriction fragment length polymorphism(PCR-RFLP) technique was used to analyze the genotypes of CYP1A1 gene Msp I site in 80 subjects of Mongolian nationality and 120 subjects of Han nationality among whom there is no blood relationship each other.

RESULTSThe genotype frequency of CYP1A1 gene Msp I site showed that the wild-type, heterozygote, homozygous variants were 35.0%, 48.7%, 16.3% and 33.3%, 52.5%, 14.2% respectively distributions of Mongolian nationality and Han nationality population, and the Chi-square tests showed that there was no significant difference between the two groups.

CONCLUSIONThe genotype frequency distributions of CYP1A1 gene Msp I site did not exhibit the obvious difference between Mongolian nationality and Han nationality population of Inner Mongolia.

Adolescent ; Adult ; Aged ; Binding Sites ; genetics ; China ; Cytochrome P-450 CYP1A1 ; genetics ; Deoxyribonuclease HpaII ; metabolism ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Mongolia ; ethnology ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; Young Adult

OBJECTIVETo investigate the association of activated coagulation factor VII(F7a) and its gene Msp I polymorphism with coronary heart disease in elderly patients.

METHODSThis was a case-control study, and the method of candidate gene was adopted. F7 genotypes were identified with polymerase chain reaction amplified genomic deoxyribonulieic acid (DNA) and Msp I restriction fragment length polymorphism analysis, and the level of plasma F7a was detected with recombinant tissue factor method for 108 elderly patients with coronary heart disease and 120 sex- and age-matched healthy control subjects.

RESULTS(1) Plasma F7a levels was significantly higher in elderly patients with coronary heart disease than in healthy control subjects (2.88 +/- 0.62 vs 2.58 +/- 0.60 microg/L, P < 0.05), and was significantly higher in old myocardial infarction than in stable angina pectoris (3.12 +/- 0.62 vs 2.76 +/- 0.60, P < 0.05). F7a was shown to be a risk factor for coronary heart disease in elderly patients by Logistic regression analysis (OR=1.21 P < 0.05). (2) The allelic frequencies were in accordance with Hardy-Weinberg equilibrium. The results suggested that the distribution of genotype and allelic frequencies in the groups displayed no significant difference, and there was no difference between the subgroups of coronary heart disease in elderly patients, either (P > 0.05). (3) F7a level was significantly higher in RR genotype than in Q allele carriers (2.72 +/- 0.60 vs 1.98 +/- 0.59 microg/L, P < 0.05) and was associated with F7 gene polymorphism.

CONCLUSIONPlasma F7a level may be an independent risk factor of coronary heart disease in elderly patients, and it may be influenced by the Msp I polymorphism of F7 gene.

Aged ; Binding Sites ; genetics ; Case-Control Studies ; Coronary Disease ; blood ; genetics ; Deoxyribonuclease HpaII ; metabolism ; Factor VII ; genetics ; metabolism ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

OBJECTIVETo observe the relationship between skewed X-chromosomal inactivation (SXCI) and development of lung cancer in females.

METHODSDNA was isolated from peripheral blood cells from patients with primary lung cancer (n = 148) and control subjects (n =289). Exon 1 of androgen receptor ( AR) gene was amplified, with its products from different alleles resolved on denaturing polyacrylamide gels and visualized by silver staining. The corrected ratio (CR) between products from different AR alleles before and after Hpa II pretreatment was calculated. All statistical tests were two-sided.

RESULTSWith CR> or = 10 adopted as the criterion, SXCI was found more frequently in the younger patients ( C50 years; 7. 9%) than in the controls of the same age group (1. 2% ; P = 0. 046). The SXCI frequency, however, were not significantly different between the old patients ( > 50 years; 4. 5% ) and the controls of the same age group (5. 4% ; P =0. 488). Whether taking CR> or =3 or CR> or =10 as the criteria, the average ages of the patients with SXCI were more than 10 years younger than those without SXCI (P < 0. 05).

CONCLUSIONSXCI in blood cells is associated with early development of lung cancer in females.

Adult ; Age Factors ; Aged ; Alleles ; Chromosomes, Human, X ; genetics ; DNA ; genetics ; metabolism ; Deoxyribonuclease HpaII ; metabolism ; Exons ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms ; blood ; genetics ; pathology ; Middle Aged ; Polymerase Chain Reaction ; Receptors, Androgen ; genetics ; X Chromosome Inactivation