PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Gene mutation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1992

Polymerase chain reaction and other methods to detect hot-spot and multiple gene mutations.

Gene mutations responsible for main genetic diseases as Duchenne/Becker muscular dystrophy or cystic fibrosis, and involved in more important diseases like cancer or cardiac diseases have been identified. Direct DNA tests can now be performed for these disorders. However, despite the knowledge of the exact alteration of the DNA sequence in these diseases, incorporating DNA analysis into large screening programs has been hindered by technical difficulties since each different mutation requires a different probe to be detected. To overcome these problems the polymerase chain reaction technique (PCR) has been proposed. Multiplex PCR procedure is possible and consists of simultaneously amplifying several separate DNA sequences (the upper limit of the number of multiplex reactions that can be executed at one time is not known; eight or nine separate DNA sequences amplified have already been described). Another approach is to directly sequence the gene mutations generally concentrated in 'hot-spot' regions. This way it is possible to identify numerous mutations using only one micro-sequencing reaction (50-100 nucleotides). New generations of very sophisticated systems like capillary electrophoresis or non-isotopic, but very sensitive, microsequencing systems should allow in a near future to withdraw the use of PCR for this purpose.

Base Sequence↗
PubMed1977

Induction of gene mutations and gene conversions by vinyl chloride metabolites in yeast.

Chloroethylene oxide and 2-chloroacetaldehyde, two metabolites of vinyl chloride, and 2-chloroethanol, a putative metabolic intermediate, were assayed for their genetic activity in the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae. Chloroethylene oxide was found to be the most effective in inducing forward mutations in Sch. pombe and gene conversions in S. cerevisiae, increasing the mutation and conversion frequencies 340 and 50 times, respectively, over those of the controls. In either the presence or the absence of mouse liver microsomes, 2-chloroacetaldehyde showed only feeble genetic activity, and 2-chloroethanol was completely inactive in both yeast strains. In contrast to vinyl chloride, 2-chloroacetaldehyde did not induce forward mutations in Sch. pombe inthe host-mediated assay in mice. The results strongly support the hypothesis that chloroethylene oxide is one of the principal mutagenic agents formed from vinyl chloride in the presence of mouse liver enzymes.

Acetaldehyde↗
PubMed1979

[Comparative study of mutator-gene prv and several other mutator-genes of Escherichia coli K-12].

Mutations prv1, prv2 and mutR34, increasing frequencies of intragenic recombinations, are found not to complement and therefore to be alleles of one gene. Checking for the influence of mutator genes mutS3, mutT1 and uvrE502 on the intragenic recombination in conjugational crossings has shown that mutators mutS3 and uvrE502 increase the frequency of intragenic recombinations while mutT1 does not change it. None of the examined mutator genes influence the conjugational frequencies of recombination. A supplementary analysis for the mutability of the mutant prv1 has been carried out. The prv1 mutation can induce mutations of the frameshift type. Mutations uvrA6, recB21, recC22 and lexA produce no influence on the display of a mutator effect of the prv1 mutation.

Conjugation, Genetic↗
PubMed2024

Predictive modeling of gene mutations for the survival outcomes of epithelial ovarian cancer patients.

Epithelial ovarian cancer (EOC) has a low overall survival rate, largely due to frequent recurrence and acquiring resistance to platinum-based chemotherapy. EOC with homologous recombination (HR) deficiency has increased sensitivity to platinum-based chemotherapy because platinum-induced DNA damage cannot be repaired. Mutations in genes involved in the HR pathway are thought to be strongly correlated with favorable response to treatment. Patients with these mutations have better prognosis and an improved survival rate. On the other hand, mutations in non-HR genes in EOC are associated with increased chemoresistance and poorer prognosis. For this reason, accurate predictions in response to treatment and overall survival remain challenging. Thus, analyses of 360 EOC cases on NCI's The Cancer Genome Atlas (TCGA) program were conducted to identify novel gene mutation signatures that were strongly correlated with overall survival. We found that a considerable portion of EOC cases exhibited multiple and overlapping mutations in a panel of 31 genes. Using logistical regression modeling on mutational profiles and patient survival data from TCGA, we determined whether specific sets of deleterious gene mutations in EOC patients had impacts on patient survival. Our results showed that six genes that were strongly correlated with an increased survival time are BRCA1, NBN, BRIP1, RAD50, PTEN, and PMS2. In addition, our analysis shows that six genes that were strongly correlated with a decreased survival time are FANCE, FOXM1, KRAS, FANCD2, TTN, and CSMD3. Furthermore, Kaplan-Meier survival analysis of 360 patients stratified by these positive and negative gene mutation signatures corroborated that our regression model outperformed the conventional HR genes-based classification and prediction of survival outcomes. Collectively, our findings suggest that EOC exhibits unique mutation signatures beyond HR gene mutations. Our approach can identify a novel panel of gene mutations that helps improve the prediction of treatment outcomes and overall survival for EOC patients.

Humans↗
PubMed1991

Overview: industrial perspectives on existing in vivo gene mutation assays.

In vivo gene mutation assays are considered the most definitive for the evaluation of human health risks. Suggestions are provided here for the critical evaluation of the application of established in vivo gene mutation assays and alternative approaches in the evaluation of industrial chemicals. Objective evaluation of the assays and approaches based on sound science and practical issues will allow better application of the existing assays. Such an evaluation may also help illuminate areas of improvement, as well as help guide the development of future assays.

Animals↗
PubMed1975

Mutator genes and selection for the mutation rate in bacteria.

Gene frequencies in populations of haploid, asexual organisms are described by linear recurrence equations. Several models in which the mutation rate is controlled by one locus and the fitness is controlled at one or more other loci are developed. It is shown that good approximations can be introduced to give explicit solutions for the course of selection in these models. It is shown that a strong non-equilibrium selection for mutator genes is possible even when the presence of such a gene decreases the fitness of an individual. Experiments that corroborate these conclusions are discussed along with the effects of population size that determine the applicability of these results to natural populations.

Alleles↗
PubMed1992

Frequent association of p53 gene mutation in invasive bladder cancer.

Structural alterations of the p53 gene were investigated to elucidate the molecular biological difference between superficial and invasive bladder cancer by polymerase chain reaction single-strand conformation polymorphism analysis. In 25 bladder cancers obtained from 23 patients, p53 gene mutations were investigated in exon regions 4 to 11. Twenty-four were transitional cell carcinomas, and the remaining one was a squamous cell carcinoma. Only one of 13 superficial bladder cancers, including pTis, pTa, and pT1, was found to have p53 gene mutation. However, of 12 invasive bladder cancers with pT2, pT3, and pT4, six primary carcinomas, including a squamous cell carcinoma and one metastatic carcinoma, were found to have p53 gene mutations. The number of cancers examined in Grades 1, 2, and 3 was three, seven, and 15, respectively. p53 gene mutation was not found in any of the ten cancers with Grades 1 and 2, while eight of 15 bladder cancers with Grade 3 were found to have p53 gene mutation. The results indicated that the incidence of p53 gene mutations appeared to be much higher in invasive-type and high-grade bladder cancers than in superficial and low-grade ones. Our results are compatible with the recently published results by Sidransky et al. [Science (Washington DC), 252: 706-709, 1991] showing that p53 gene mutations were frequently found in invasive bladder cancers by sequence analysis on polymerase chain reaction amplified products corresponding to exons 5 to 9. Our results are also compatible with previously reported results by Olumi et al. (Cancer Res., 50: 7081-7083, 1990) showing that the loss of chromosome 17p, revealed by analysis with restriction fragment length polymorphism, was frequent in high-grade bladder cancers. In this study, p53 gene mutations were often found in exon 4 as well as in other exons. Therefore, this region should also be examined for screening of mutations of this gene in bladder cancer. There appeared to be no consistent mutation sites in exons 4 to 11 of the p53 gene and no specific patterns of the mutation in bladder cancer.

Base Sequence↗
PubMedDate not supplied

Oligotriche and quaking gene mutations. Phenotypic effects on mouse spermatogenesis and testicular steroidogenesis.

The phenotypic actions of the oligotriche gene mutation on testicular function have not been elucidated, although it is known that male mice homozygous for the mutation are infertile. In the present study, the effect of the oligotriche gene mutation on mouse testicular function was analyzed by comparing normal and mutant mice. Spermatogenesis was analyzed by enumerating germ cells in seminiferous tubules at specific stages of spermatogenesis and by electron microscopy. Steroidogenic potential was estimated by radioimmunometric determination of testosterone secreted by testes perfused in vitro. Parallel studies were completed for male mice homozygous for the quaking gene mutation, a mutation known to cause male mouse sterility by disrupting sperm tail development. The experimental results suggest that the oligotriche and quaking gene mutations interfere with sperm tail formation by different mechanisms. Testicular steroidogenesis was not affected by either gene mutation. The results provide the first evidence that the oligotriche gene mutation induces male mouse sterility by effecting the complete absence of a sperm tail. This phenotypic action is different from that of the quaking gene mutation.

Animals↗
PubMed2026

Metagenomic Deep Sequencing Identifies Gene Mutations Associated with Chemotherapeutic Resistance in Vitreoretinal Lymphoma.

PURPOSE: To identify gene mutations associated with chemotherapeutic resistance in patients with vitreoretinal lymphoma (VRL) using metagenomic deep sequencing (MDS) of intraocular specimens. METHODS: Patients with VRL confirmed by cytopathology and immunohistochemistry, flow cytometry, and/or polymerase chain reaction for MYD88, were included. Intraocular specimens underwent MDS of the host genome. Gene mutations were identified and cross-referenced with the Catalogue of Somatic Mutations in Cancer database to determine associations with chemotherapeutic resistance. RESULTS: Forty-nine patients with VRL underwent MDS, with six specimens from four patients revealing eight gene mutations associated with chemotherapeutic resistance. Four specimens from three patients harbored mutations associated with methotrexate resistance, the mainstay of VRL treatment. In one patient, serial sampling from the initial vitrectomy and two subsequent recurrences revealed distinct resistance-associated mutations at each time point. Despite multi-agent therapy including rituximab, consolidation regimens, and lenalidomide, this patient ultimately succumbed to the disease, whereas the other three patients remained in long-term remission. CONCLUSIONS: Our findings demonstrated that specific gene mutations associated with chemotherapeutic resistance may be harbored by VRL. The detection of different resistance mutations at sequential time points in one patient may reflect clonal selection, treatment pressure, or variable detection sensitivity. The ability to easily sample ocular fluid and detect different mutations associated with tumor recurrence or persistence may provide insights into tumor pathogenesis and could inform prognosis and influence treatment decisions. These findings establish a foundation for developing targeted PCR assays for identified resistance genes, which could transform clinical practice in VRL.

Chemotherapeutic resistance-associated mutations↗
PubMed1992

p53 gene mutation spectrum in hepatocellular carcinoma.

In order to clarify the significance of mutation of the p53 tumor suppressor gene in the genesis and development of human hepatocellular carcinoma (HCC) in an aflatoxin B1 low-exposure area, the spectrum, i.e., incidence, type, and site, of p53 gene mutations was examined in 169 tissue samples resected mainly from Japanese patients using single-strand conformation polymorphism analysis and direct sequencing. Forty-nine tumors (29%) showed a p53 mutation (39 point mutations and 10 frameshifts). The point mutations comprised 18 transitions, only 4 of which occurred at CpG sites, and 21 transversions. Two evolutionarily conserved domains, IV and V, contained 65% of all mutations and codon 249 was the most frequent mutation site (7/49). The spectrum of p53 mutation did not differ among HCCs in relation to the type of hepatitis virus infection, sex, age, and background liver disease of patients, tumor size, or presence of metastasis, but incidence and site were significantly associated with the degree of differentiation of cancer cells. In poorly differentiated HCC, p53 mutation was frequent (54%) and clustered on domains IV and V, whereas in well or moderately differentiated HCC, the mutation was less frequent (21%) and equally distributed on domains II to V. Restriction fragment length polymorphism analysis revealed loss of heterozygosity on chromosome 17p in 55 (69%) of 80 informative cases and in 34 (95%) of 36 cases with p53 mutation. Therefore, p53 gene mutation is suggested to occur independently of the type of viral infection or status of preexisting liver disease and to occur preferentially in moderately and poorly differentiated HCCs in association with or after loss of another p53 allele as a late event of HCC progression.

Adult↗
PubMed1992

[Tumor suppressor genes: mutations in RB and p53 genes are significant carcinogenic factors].

The RB and p53 tumour suppressor genes encode nuclear proteins that exert an inhibitive effect on cell growth. A large variety of human tumour types manifest loss or mutation of the RB or p53 genes, and p53 mutation is the commonest genetic alteration found in tumour cells. In addition, the RB and p53 proteins may be inactivated by complex formation with viral oncoproteins--for instance, in the case of cervical carcinoma carrying human papilloma virus. In vivo introduction of an intact RB or p53 gene into malignant cells lacking the respective gene results in suppression of the neoplastic phenotype and thus of tumourigenicity, p53 being the more potent of the two in this respect. Further elucidation of tumour suppressor genes may well result in future improvement in the diagnosis and treatment of cancer.

Genes, Retinoblastoma↗
PubMed1992

Detection of p53 gene mutations in human ovarian and endometrial cancers by polymerase chain reaction-single strand conformation polymorphism analysis.

The presence of mutations in the p53 gene was examined in ovarian cancers by a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. The primers were designed to amplify exons 5 through 9 that contain phylogenetically conserved domains of the p53 gene. Mutations were detected in 5 out of 10 cases, one of which contained a deletion in the second allele. A single base substitution was detected in 4 cases at codons 162, 175, 205 and 273 and a single base insertion in one case within codon 315. A high frequency of p53 mutations in ovarian cancers and lack of mutation in 6 benign ovarian tumors and 2 normal ovaries suggested that the mutation of the p53 gene was associated with the genesis and/or progression of ovarian cancer. In 1 of 7 endometrial cancers, two mutations at codons 239 and 254 were detected.

Alleles↗
PubMed1975

Induction of gene mutations and chromosomal aberrations by simian virus 40 in cultured mammalian cells.

Induction of gene mutations by SV40 was studied in aneuploid human and Chinese hamster cells. In Chinese hamster cells SV40-induced chromosome aberrations were also studied. SV40 penetrated into the cells of both lines and induced synthesis of the T antigen. The efficiency of infection in Chinese hamster cells was tested additionally by their ability to form colonies in medium lacking the serum growth factor. The maximal number of cells with serum growth factor independence was observed on the first day after infection. When hamster cells had been maintained in "factor-free medium" for the first two passages after infection a sub-line was isolated, which synthesized T antigen 60 days after exposure to SV40. This was considered to be an indirect proof of the integration of viral genome into host chromosome. A significant increase in the frequency of chromosomal aberrations was detected in SV40-infected Chinese hamster cells. It was observed on the first and second days after treatment. The most numberous were the chromosome and chromatid breaks, which were distributed randomly in 5 morphological groups according to the chromosome length. SV40-induced mutations of resistance to 8-AG and 6-MP in human and Chinese hamster cells respectively were detected, when cells were plated in selective medium one to five days after infection. Induction was detected in all the 4 experiments with human cells and in 9 out of 11 experiments with Chinese hamster cells. Induction was highly significant according to the Wilcoxon test (P greater than 0.99), when the results of all experiments carried out in human and Chinese hamster cells were summarized. Resistance was stable after prolonged cultivation of 13 isolated clones under non-selective conditions. It is suggested that viral genome integration, gene mutations and chromosomal aberrations may have common molecular mechanisms. The role of gene mutations in virus-induced carcinogenesis is discussed.

Aneuploidy↗
PubMed1992

Detection of ras gene mutations in human lung cancer: comparison of two screening assays based on the polymerase chain reaction.

We studied the prevalence of point mutations in ras oncogenes (K-ras and N-ras) in DNA from white blood cells and tumor tissue from 36 untreated patients with non-small-cell lung cancer, all of whom were smokers or ex-smokers. We observed somatic K-ras mutations in one-third of the lung carcinomas studied but no N-ras mutation. K-ras codon 12 mutations were found more frequently in adenocarcinomas than in the other histopathological subtypes studied. More than 60% (10/16) of the lung adenocarcinomas had a codon 12 mutation, most of which were G to T transversions. No mutations was found in white blood cell DNA. Two polymerase chain reaction screening methods, oligonucleotide hybridization and denaturing gradient gel electrophoresis (DGGE), were used to detect the mutations. The oligonucleotide method appears to be more sensitive than DGGE, but DGGE proved to be a reliable nonradioactive method for rapid screening of point mutations in genes relevant to carcinogenesis.

Adenocarcinoma↗
PubMed1979

An assay for histocompatibility gene mutations in mice.

A method used for detecting histocompatibility gene mutations by tailskin graft tests in mice is described. Advantages and disadvantages are found for this assay system. The results of published work point to some interesting features of the H-gene mutational event, but also leave many questions yet to be answered.

Animals↗
PubMed1992

High incidence of p53 gene mutation in human ovarian cancer and its association with nuclear accumulation of p53 protein and tumor DNA aneuploidy.

Using the polymerase chain reaction and single-strand conformation polymorphism analysis, p53 gene mutations were examined in 24 cases of ovarian tumor including 14 ovarian carcinomas and 2 borderline cases of common epithelial type, 7 germ cell tumors, and one stromal tumor. Abnormal bands indicating mutations were detected in 12 (50%) of the cases examined, being present most frequently in common "epithelial" ovarian carcinoma (71%, 10/14). One case each of squamous cell carcinoma originating in a dermoid cyst and anaplastic dysgerminoma were positive for mutation. Direct sequencing confirmed 12 mutations and revealed G-->A and G-->C nucleotide changes in 5 and 3 cases (42% and 25%), respectively. The mutation was localized at the CpG site of the gene in 3 cases. Immunohistochemical examination of p53 protein in 21 cases and DNA flow-cytometrical analysis in 17 cases were also performed. Nuclear accumulation of the p53 protein and DNA aneuploidy pattern were detected in 11 (52%) and 9 (53%) cases, respectively. These were significantly correlated with p53 gene mutation (P < 0.01 and P < 0.05, respectively; Fisher's exact test). Neither mutation of the p53 gene, nuclear accumulation of p53 protein nor DNA aneuploidy was detected in borderline cases of common "epithelial" type, typical dysgerminoma and immature teratoma. These results suggest that p53 gene mutation, nuclear accumulation of the protein and the DNA aneuploidy pattern are events occurring almost simultaneously in the progression of ovarian tumors, and that p53 abnormalities seem to be correlated with a high grade of malignancy.

Aneuploidy↗
PubMed1991

Chemical induction of somatic gene mutations and chromosomal aberrations in lung fibroblasts of rats.

Rats can be used to detect both somatic gene mutations and chromosomal aberrations induced in vivo. The technique adapted from Chinese hamsters for the isolation and analysis of lung fibroblasts confirm the surprising results obtained in hamsters; namely, methyl methanesulphonate induces many micronuclei but no significant increase in gene mutations. In contrast ethylnitrosourea induces both micronuclei and gene mutations.

Animals↗