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Results for “Point Mutation”

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At least 217 records · Page 12Linked to original sources
PubMed1993

K-ras and p53 point mutations in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced hamster lung tumors.

Lung tumors were induced in Syrian golden hamsters by s.c. injection of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). After 40 weeks lung tumor tissue was isolated. Administration of the NNK and exposure of the animals to an atmosphere of 65% oxygen resulted in a statistically significant reduction in tumor size but did not alter the histological tumor type or tumor incidence when compared with carcinogen treated animals maintained under ambient air. Histologically, lung tumors had the morphologic features of adenomas and adenocarcinomas with approximately 15% being squamous cell carcinomas. Lung tumors were examined for mutations in the Ki-ras oncogene and the p53 tumor suppressor gene by direct sequencing. The Ki-ras mutation frequency in RNA isolated from pooled tumors and in DNA isolated from individual tumors were found to be identical. Activated Ki-ras alleles were detected in 77-94% of tumors. All mutations observed (from a total of 65) except one were GC-AT. The Ki-ras mutations resulted in amino acid substitutions at either codons 12 or 13. No mutations were detected at the 61st codon. Examination of the same tumors for p53 mutations showed only one point mutation. We conclude that the NNK treatment in Syrian golden hamsters results in a distinctive mutation pattern in the Ki-ras gene whereas p53 gene mutations may not play a major role at this stage in hamster lung tumorigenesis.

Animals↗
PubMed2006

Detection of known thalassemia point mutations by snapback single-strand conformation polymorphism: the feasibility analysis.

OBJECTIVES: To explore if snapback single-strand conformation polymorphism (snapback SSCP) can be applied to the detection of known thalassemia point mutations. DESIGN AND METHODS: We examined 13 types of known thalassemia point mutations by using snapback SSCP. RESULTS: These 13 different thalassemia point mutations could be identified by snapback SSCP. CONCLUSIONS: Snapback SSCP can be applied to the detection of known thalassemia point mutations. The advantages of snapback SSCP are (1) it is simple as compared to PCR-ASO; (2) snapback SSCP is specific and stable once the conditions of snapback SSCP are optimized; (3) samples can be checked at any time without the limit of half-life of radioactive isotope; and (4) since PCR products used in snapback SSCP can be checked by using 2% agarose gel before snapback SSCP, misdiagnoses caused by false positive or false negative PCR can be reduced significantly in snapback SSCP.

Base Sequence↗
PubMed2000

Point mutations in mitochondrial DNA of patients with alcoholic cardiomyopathy.

The pathogenesis of alcoholic cardiomyopathy (ACM) is not well understood. However, recent reports have shown that mutations in mitochondrial DNA (mtDNA) were associated with mitochondrial encephalomyopathy and cardiomyopathy. Our objective was to explore point mutations in mtDNA and the pathogenesis of ACM. We obtained heart biopsy specimens from ten male habitual drinkers with congestive heart failure. We amplified the total mtDNA obtained from these specimens using a two-step polymerase chain reaction method and analyzed the products using automated fluorescence-based direct sequencing. The sequences were compared with those of controls. MtDNA from the ACM patients contained multiple point mutations. Specifically, four of the ten patients carried five point mutations that had been detected previously in several other mitochondrial diseases. These point mutations were not observed in controls. These results suggest that mtDNA abnormalities are involved in the pathogenesis of ACM.

Adult↗
PubMed1994

A point mutation responsible for human erythrocyte AMP deaminase deficiency.

A point mutation of C to T on the human erythrocyte AMP deaminase gene (AMPD-3) has been identified by molecular analysis of the genetic materials from the enzyme deficient individuals. Four separate DNA fragments covering the entire coding region of AMPD-3 cDNA were amplified using polymerase chain reaction (PCR) technique and sequenced directly. The same point mutation was detected in both of the two B-lymphoblast cell lines derived from the complete deficiency of human erythrocyte AMP deaminase: a single nucleotide substitution of C to T resulted in an amino acid change of Arg to Cys at the codon 573. The analysis of genomic DNA demonstrated that two individuals with complete deficiency were homozygous for the detected mutation, and two individuals with partial deficiency were diagnosed as heterozygous. This mis-sense mutation reads to a catalytically inactive enzyme.

AMP Deaminase↗
PubMed1995

A point mutation, C to T, in exon 8 of the porphobilinogen deaminase gene in a Japanese family with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized by a deficiency of porphobilinogen deaminase (PBGD). To date, only two mutations have been reported in Japanese patients. We report here another mutation of the gene in a Japanese patient. Analysis of the PCR amplified DNA fragments of the gene by direct-sequencing method revealed the gene abnormality responsible for the disease. The mutation found was a point mutation, C to T, in exon 8 of the gene at position 346 of the housekeeping cDNA from the translation codon ATG. This mutation resulted in an Arg116 to Trp substitution. Four carriers in the family were successfully diagnosed by detecting the mutation using restriction analysis of PCR products.

Adult↗
PubMed2002

[A new point mutation on exon 2 of parkin gene in Parkinson's disease].

OBJECTIVE: To detect the relationship between point mutations on exon 2 of parkin gene and sporadic early-onset Parkinson's disease. METHODS: The point mutations on exon 2 of parkin gene were detected using polymerase chain reaction(PCR), agarose electrophoresis, single strand conformation polymorphism(SSCP), DNA sequencing and analysis of restrict enzyme in DNA of 60 Parkinson's disease patients with an onset age under 50 and 120 normal controls. RESULTS: One homozygous mutation (G(237)-->C) on exon 2 was found by sequencing and verified by analysis of restrict enzyme, whereas no mutation was found in normal controls. CONCLUSION: Point mutations on exon 2 of parkin gene are likely to be related to sporadic early-onset Parkinson's disease.

Adult↗
PubMed1993

Roles of evolution, quantum mechanics and point mutations in origins of cancer.

The fact point genetic lesions--which provide the species with an ability to respond favorably to changing environmental conditions--are also specifically compatible with "activating" point mutation sensitive, evolutionarily conserved proto-oncogenes and gene p53 implies an additional function for evolutionary processes. In particular, this suggests that evolutionary point lesions may also be designed to remove from the gene pool those genomes which have accumulated advanced levels of evolutionary-induced mutations, thereby protecting the species from the adverse consequences of accumulating mutations beyond an unsafe upper limit. This hypothesis is used to construct a mutation model polynomial for incidence of human cancer as a function of age. The model assumes that point lesion sensitive proto-oncogenes and "p53-type" genes are evolutionarily conserved and must exhibit wild-type genetic information at fertilization for proper growth. Subsequently, evolutionary lesions populate these conserved domains, eventually causing point lesion sensitive genes to yield amino acid substituted proteins capable of participation in transforming normal cells to cancer. The mechanism for evolutionary base substitutions is a time-dependent Topal-Fresco process in which the required unusual tautomers are provided by proton exchange tunneling (see, W.G. Cooper, 1992a). The very good agreement between incidence of cancer data and the model is consistent with the hypothesis that duplex DNA has been evolutionarily designed to supplying an optimum rate of point mutation variation for purposes of (a) providing the species with the ability to respond favorably to changing environmental conditions and (b) to protect the species from adverse consequences of accumulating excessive mutations. (e.g., W.G. Cooper, 1992b). As a result of identifying "tunneling sensitive" DNA codes, consequences of evolutionary lesions in diploid and haploid human genomes are evaluated. The "faster evolving" oocyte genome may be responsible for most evolutionary traits, whereas evolutionarily conserved domains may be supplied by the "slower evolving" male haploid genome. Evidence from fragile X genetic systems support this conclusion. The model further illustrates how fragile X genetic properties could be a result of evolutionary lesions altering genetic specificities of "tunneling sensitive" CGG codes to specify DNA synthesis initiation codons, CUG or UUG. This could cause reinitiation of DNA synthesis and the addition of more CGG codes to the "tunneling sensitive" segment of consecutive (CGG)n repeats which would explain how (CGG)n segments are "expanded" during oogenesis.

Age Factors↗
PubMed2003

[Study on a new point mutation of nt3426 A --> G of mitochondrial DNA in a diabetes mellitus family].

OBJECTIVE: To elucidate the relationship between point mutations of nt3243A --> G, nt3426 A --> G of mitochondrial DNA and type 2 diabetes mellitus(DM). METHODS: Two hundred patients with type 2 DM and 180 controls with normal glucose tolerance and absence of DM family history were included. The mutations were determined by PCR-restriction fragment length polymorphism. RESULTS: The point mutation nt3426A --> G of mitochondrial DNA ND1 was found in 2 of the patients with type 2 DM (1.0%) but in none of the controls (0). The incidence of this mutation showed no significant difference between the two groups(P>0.05). And none was found to have the mutation of nt3243 --> G. CONCLUSION: The point mutation nt3426 A --> G of mitochondrial DNA ND1 may not be an independent factor to cause type 2 DM.

Adult↗
PubMed2001

Ehlers-Danlos syndrome type IV with a unique point mutation in COL3A1 and familial phenotype of myocardial infarction without organic coronary stenosis.

We report on a 43-year-old male patient with Ehlers-Danlos syndrome (EDS) type IV with acute myocardial infarction (MI) without organic coronary stenosis. The disease was complicated with pneumothorax, subcutaneous and mediastinal emphysema, and splenic artery rupture. Three of the patient's family members suffered sudden cardiac death or MI. A diagnosis of EDS type IV was confirmed by decreased production of type III collagen by 86%. Mutation analysis revealed a point mutation in the COL3A1 gene that substituted glycine for aspartate at amino acid position 877. This mutation had not been reported as pathogenic for EDS type IV. These findings suggest close linkage between the mutation and the phenotype with familial MI.

Adult↗
PubMed2004

Heparanase mRNA expression and point mutation in hepatocellular carcinoma.

AIM: To explore the expression of heparanase mRNA and point mutation in hepatocellular carcinoma (HCC). METHODS: Reverse transcription polymerase chain reaction was used to measure the expression of heparanase mRNA in the primary tumor tissues and surrounding liver tissues of 33 HCC patients. T-A cloning and sequencing were used to detect whether there was any mutation in the amplified PCR products. RESULTS: The expression of heparanase mRNA was positive in 16 primary tumor tissues of HCC, and the positive rate was 48.5%, which was significantly higher than that in the surrounding liver parenchyma (P<0.01). The positive rate for heparanase gene in high-tendency to metastatic recurrence group (71.4%, 10/14) was obviously higher than that in low-tendency to metastatic recurrence group (31.6%, 6/19) (P = 0.023). The positive rate for heparanase gene in patients with metastatic recurrence during postoperative follow-up (78.6%, 11/14) was also significantly higher than that in those without metastatic recurrence (21.4%, 3/14) (P = 0.003). Sequence analysis of the HPA PCR products was made in 7 patients, and 2-point mutations were found in 4 patients, one of which was sense mutation, neither base insertion nor deletion was detected. The mutation rate was 57.1% (4/7). CONCLUSION: The expression rate of heparanase mRNA increases in HCC, and HPA mRNA may be one of the reliable markers for the metastatic activity gained by the liver tumor cells and could be used clinically in predicting metastatic recurrence of HCC. Point mutation may be one of the causes for enhanced heparanase mRNA expression.

Base Sequence↗
PubMed1990

Point mutation in the exoplasmic domain of the erythropoietin receptor resulting in hormone-independent activation and tumorigenicity.

The receptors for erythropoietin and other cytokines constitute a new superfamily. They have no tyrosine-kinase or other enzyme motif and their signal-transducing mechanism is unclear. Here we describe two classes of activating mutations in the erythropoietin receptor (EPOR). A single point mutation in the exoplasmic domain enables it to induce hormone-independent cell growth and tumorigenesis after expression in nontumorigenic, interleukin-3-dependent haematopoietic cells. A C-terminal truncation in the cytoplasmic domain of the EPOR renders the receptor hyperresponsive to erythropoietin, but is insufficient to induce hormone-independent growth or tumorigenicity. The activating point mutation retards intracellular transport and turnover of the receptor. These alterations in metabolism and tumorigenicity caused by the EPOR with activating point mutations are similar to those observed in erythropoietin-independent activation of the wild type EPOR by association with gp55, the Friend spleen focus-forming virus glycoprotein.

Amino Acid Sequence↗
PubMed1999

Additional value of K-ras point mutations in bronchial wash fluids for diagnosis of peripheral lung tumours.

The purpose of this study was to examine the additional diagnostic value of K-ras point mutations in the clinical diagnosis of peripheral lung tumours. To this end, bronchial wash fluids obtained during bronchoscopy from patients suspected of having lung cancer were studied. Only those patients were investigated for whom the cytological diagnosis was not conclusive for malignancy. As a control group, patients without lung cancer were investigated. The method of "point mutation detection using the exonuclease amplification coupled capture technique" (Point-EXACCT) for analysis of K-ras codon 12 was performed in bronchial wash fluids and the corresponding tumour tissue, if available. K-ras point mutations were identified in 4 out of 19 (21%) bronchial wash fluids from patients without a decisive diagnosis of malignancy. The diagnosis of malignancy was further based on cytological examination of bronchial brush specimens, perthoracic needle aspiration, histological investigation of biopsy and resection specimens, needle aspiration of a lymph node in the neck and pleural fluid examination. Four of the patients who were K-ras-positive yielded positive malignant tissue via bronchoscopy even though the bronchial wash was negative for malignancy. The bronchial wash was positive for K-ras in two of the four patients whose tumour tissue demonstrated the K-ras mutations. Analysis of bronchial wash fluids from 11 patients without lung cancer revealed no K-ras codon 12 mutations. In conclusion, K-ras point mutations can be identified in bronchial wash fluids obtained during bronchoscopic procedures. K-ras can be used as a biomarker in the clinical diagnosis of lung cancer and may serve as an adjunct to cytology in lung cancer diagnosis.

Aged↗
PubMed1999

Demonstration of the pathogenic effect of point mutated keratin 9 in vivo.

A wild type keratin 9 (K9) cDNA and a point mutated keratin 9 cDNA were injected subcutaneously into mouse skin. The hemagglutinin tag staining of the wild type K9 cDNA injected specimens mainly showed a homogeneous pattern, whereas the point mutated K9 cDNA injected specimens mainly showed a granular pattern in the suprabasal cells. Double staining of K9 and the endogenous keratin revealed the incorporation of de novo synthesized K9 into the keratin network. These results demonstrate that (1) a naked DNA transfection into mouse skin can detect the pathogenic changes of point mutated keratin in vivo and (2) the keratin 9 mutation disrupts the keratin network formation in the suprabasal cells in vivo.

Animals↗
PubMed1995

p53 deficiency does not affect the accumulation of point mutations in a transgene target.

DNA repair is required by organisms to prevent the accumulation of mutations and to maintain the integrity of genetic information. Mammalian cells that have been treated with agents that damage DNA have an increase in p53 levels, a p53-dependent arrest at G1 in the cell cycle, and a p53-dependent apoptotic response. It has been hypothesized that this block in cell cycle progression is necessary to allow time for DNA repair or to direct the damaged cell to an apoptotic pathway. This hypothesis predicts that p53-deficient cells would have an abnormal apoptotic response and exhibit a "mutator" phenotype. Using a sensitive assay for the accumulation of point mutations, small deletions, and insertions, we have directly tested whether p53-deficient cells exhibit an increased frequency of mutation before and after exposure to DNA-damaging agents. We report that wild-type and p53-deficient fibroblasts, thymocytes, and tumor tissue have indistinguishable rates of point mutation accumulation in a transgenic lacI target gene. These results suggest that the role of p53 in G1 checkpoint control and tumor suppression does not affect the accumulation of point mutations.

Animals↗
PubMed2006

[Study of p16INK4/CDKN2 gene homozygous deletions and point mutation in squamous cell carcinoma of buccal mucosa].

OBJECTIVE: To explore the correlation between homozygous deletions and mutation of p16 gene and the carcinogenesis and progression of squamous cell carcinoma of buccal mucosa. METHODS: Thirty buccal cancers, 10 leukoplakias and 8 buccal mucosas were involved. DNA was extracted from the tissues. PCR was used to analyses homozygous deletion of p16 gene. PCR-SSCP-DNA sequencing was performed to detect the point mutation of p16 gene. Immunohistochemical techniques were used to detect the expression of P16 protein. RESULTS: Gene deletions and point mutations were not found in leukoplakia and normal buccal mucosa. Gene deletions were found in 7 samples out of 30 cases of squamous cell carcinoma of buccal mucosa (23.3%), while point mutations were found in 5 samples out of 30 cases of squamous cell carcinoma of buccal mucosa (16.7%). Sequencing analysis showed that 5 cases point mutations were missense mutations, occurred on exon 2. Three cases occurred in the same point, codon 99 (GAT --> AAT). The result of immunohistochemical stains showed that 11 out of 12 cases gene inactivation did not expressed P16 protein. CONCLUSION: Homozygous deletion and point mutation of p16 were the main pattern of gene inactivation in squamous cell carcinoma of buccal mucosa. There was a closely correlation between p16 gene inactivation and the carcinogenesis of squamous cell carcinoma of buccal mucosa.

Carcinoma, Squamous Cell↗
PubMed1996

Overexpression of the c-myc proto-oncogene in colorectal carcinoma is associated with a reduced mortality that is abrogated by point mutation of the p53 tumor suppressor gene.

The survival of 119 colorectal cancer patients was analyzed in the light of the overexpression status of the c-myc proto-oncogene mRNA and the point mutation status of the p53 tumor suppressor gene in the primary adenocarcinoma. The presence of >3 fold overexpression of c-myc mRNA in the primary tumor was found to be associated with a better prognosis than patients who evinced no overexpression (P = 0.02, log rank analysis). Point mutation of the p53 tumor suppressor gene was found to be associated with a poorer patient prognosis (P = 0.007, log rank analysis). Endogenous levels of c-myc and point mutation of p53 both contributed independently toward a poorer patient prognosis in Cox regression modeling. The better prognosis seen in patients who overexpress c-myc was offset when c-myc overexpression was coupled with a point mutated p53 gene. These results suggest that in colorectal adenocarcinoma c-myc deregulation leads to increased apoptotic death, but that this response may be modulated by a more downstream event such as point mutation of the p53 gene.

Adult↗
PubMed1996

Point mutations of the Mxil gene are rare in prostate cancers.

Overexpression of the Myc genes promote cellular transformation. Max protein exerts a pivotal function with the Myc family, and Mxi1/Mad proteins play a positive and negative activity, respectively, on transcription. The function of Mxi1 suggests that it might be a tumor suppressor protein. The Mxi1 gene map to 10p24-25 and deletions of this locus are frequently observed in prostate cancers. The N-terminal helical motif, helix-loop-helix (HLH) and leucine zipper (ZIP) regions of the Mxi1 gene are functionally important. We analyzed most of the coding region of the Mxi1 gene, including these three important regions in 32 prostate cancers and three cell lines by PCR-single strand conformational polymorphism (SSCP). To enrich neoplastic cells, the microdissection was performed on clinical samples. We detected a silent mutation in the HLH region, but no point mutations reflecting the functional change of Mxi1 were found in human prostate cancers. Point mutations of the Mxi1 gene, if they occur, must be minor events in primary prostate cancers.

Basic Helix-Loop-Helix Proteins↗
PubMed1993

The point mutation of c-Ki-ras at codon 12 in carcinoma of the pancreatic head region and in intraductal mucin-hypersecreting neoplasm of the pancreas.

In order to clarify whether the detection of a point mutation in the c-Ki-ras gene at codon 12 in tumor tissues can assist in predicting the tumor's biological grade of malignancy, two types of tumors were investigated; one was called "carcinoma in the pancreatic head region," and the other was intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN). Dot hybridization and a modified PCR technique developed by Haliassos et al. were employed. Among 16 cases of tumors in the pancreatic head region, the point mutation was detected with a high frequency only in pancreatic ductal cell carcinomas (five out of six cases, 83.3%), but was not detected in extrahepatic bile duct carcinomas (0/5) or in ampullary carcinomas (0/5). In pancreatic ductal cell carcinomas, no relation was found between the occurrence of the point mutation and the histological type of the tumor. Among 20 cases of IMHNs, the point mutation was found in 11 cases (55%). No relation was found between the occurrence of the mutation and the size of IMHNs. However, as the grade of cell atypia increased, the frequency of the mutation tended to become higher. These results suggest that detection of this point mutation might be useful for distinguishing pancreatic ductal cell carcinoma from those of other origins in the pancreatic head region, and for the determination of the histopathological grade of malignancy in IMHNs.

Aged↗