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At least 757 records · Page 42Linked to original sources
PubMed1999

[Characteristics of high frequency 249 codon mutation of p53 gene in hepatocellular carcinoma in prevalent area of China].

OBJECTIVE: To study the characteristic features of an unique hotspot missense mutation of the 249 codon of p53 gene demonstrated in human hepato-cellular carcinoma(HCC) in a region of high(Qidong) and low (Beijing) exposure to both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in China. METHODS: Surgical samples from 97 HCC from Qidong and 22 from Beijing, China, collected in 1994 through 1997, were studied. The 249 codon mutation of p53 gene was detected by PCR followed by HaeIII RFLP analysis and DNA sequencing. Intracellular p53 protein level was determined by immunohistochemical staining. RESULTS: High mutation rate of 249 codon of p53 gene was consistently found in recent years, with an average of 53.6% (52/97). No such mutation was identified in 22 Beijing HCC collected in the same time period. The genotype of p53 249 codon mutants which showed heterozygous profile was identified to be homozygous in nature following tumor tissue enrichment. Of 21 HCC shown to have 249 codon mutation, 20 exhibited high intranuclear accumulation of p53 protein. p53 protein staining was negative in the surrounding noncancerous hepatic tissue. CONCLUSION: The high frequency of homozygous mutation of the 249 codon of p53 gene accompanied with p53 protein accumulation provides important enlightenment in the understanding of hepatocarcinogenesis and clinical application of gene therapy and/or immunotherapy for HCC.

Carcinoma, Hepatocellular↗
PubMed2002

Screening of N-ras codon 61 mutations in paired primary and metastatic cutaneous melanomas: mutations occur early and persist throughout tumor progression.

PURPOSE: Mutations in the ras genes often occur during tumorigenesis. In malignant melanoma, the most common ras alterations are N-ras codon 61 mutations. This study was aimed to measure the frequency of such mutations in a large series of paired primary and metastatic melanomas to determine their role in melanoma initiation and progression. EXPERIMENTAL DESIGN: Seventy-four primary melanomas and 88 metastases originating from 54 of the primary tumors were screened for N-ras codon 61 mutations using single-strand conformation polymorphism and nucleotide sequence analyses. RESULTS: Twenty-one of the 74 primary tumors (28%) had activating N-ras codon 61 mutations. From 20 of the mutated primary tumors, a total of 34 metastases were analyzed, and all but one showed the same mutation as the primary tumor from which they originated. The remaining 53 primary tumors and corresponding metastases (n = 54) were wild-type for N-ras codon 61. Analysis of the different growth phases of the mutated primary tumors showed that the mutations were already present in the radial growth phase. Mutations were also detected in tumor-associated nevi. N-ras codon 61 mutations were associated with a higher Clark level of invasion (P = 0.012) and a lower age at diagnosis (P = 0.042) but did not affect survival (P = 0.671). CONCLUSIONS: This study shows that N-ras codon 61 mutations occur early in primary melanomas rather than in the metastatic stage and that once the mutations have occurred, they persist throughout tumor progression. This suggests that activated N-ras may be an attractive target for therapy in the subset of melanoma patients carrying such mutations.

Age of Onset↗
PubMed2002

[Optimized codon usage enhances the expression and immunogenicity of DNA vaccine encoding the HPV 6b E7 gene].

OBJECTIVE: To analyze the influence of optimal codon usage on the expression levels and immunogenicity of DNA vaccines, encoding the human papillomavirus type 6b (HPV 6b) E7 gene. METHODS: The full length E7 gene of HPV 6b was modified to substitute human preferred codon for rarely used codon, and three mutations were introduced into the pRB binding site of HPV 6b E7 to eliminate its transformation potential. The codon optimized and mutated E7 gene (hu-mE7) were cloned into the Kpn I and EcoR I site of the pcDNA3 mammalian expression vector, the in vitro expression of the hu-mE7 gene and the immunogenicity of hu-mE7 DNA vaccine were compared with the wt-E7gene. RESULTS: The in vitro expression of pcDNA3-hu-mE7 was much higher than the classical wt-E7 plasmid in monkey COS-1 cell line. Mice immunized intramuscularly with the pcDNA3-hu-mE7 showed that the codon modified E7 gene induced a stronger IFN-gamma ratios than the wt-E7 gene. CONCLUSIONS: These results suggest that the optimized codon usage contributes to the enhancement of gene expression and immunogenicity of HPV 6b E7 gene.

Animals↗
PubMed2003

Retention of the p53 codon 72 arginine allele is associated with a reduction of disease-free and overall survival in arginine/proline heterozygous breast cancer patients.

PURPOSE: The arginine to proline substitution at codon 72 represents a common aminoacidic polymorphism of the p53 protein. Recent data suggest that p53 codon 72 may modulate the response to cancer therapy. The aim of this study was to test the hypothesis that the p53 codon 72 genotype, evaluated in the tumor tissue and in the disease-free lymph node, is related to differences in disease-free and overall survival among breast cancer-affected patients. EXPERIMENTAL DESIGN: We assessed the p53 codon 72 genotype in DNA from disease-free lymph nodes and neoplastic tissues obtained from 67 women affected by breast cancer who underwent surgical resection at the Bologna Breast Cancer Surgical Unit from 1993 to 1995. RESULTS: We found that the retention of the p53 codon 72 arginine allele in the tumor tissue of proline/arginine heterozygous breast cancer patients is associated with statistically significant reduced disease-free and overall survivals. CONCLUSIONS: Our findings suggest that the genotyping for p53 codon 72 locus in both the tumor tissue and in the lymph node of breast cancer patients could contribute to identify a subset of arginine/proline heterozygous patients who have a reduced survival that is associated with the specific retention of the arginine allele in the tumor tissue.

Adult↗
PubMedDate not supplied

[The effect of intracellular concentrations of tRNA, corresponding to the rare arginine codons AGG and AGA, on the gene expression in Escherichia coli].

Influence of increased arginine concentrations of tRNA's corresponding to rare codons AGG and AGA was studied in the model system constructed earlier. The model system is a chimeric gene consisting of CAT gene fragment, part of the gene encoding for alpha-domain of beta-galactosidase E. coli and a series of synthetic inserts enriched with codons AGG and AGA. In order to increase the intracellular tRNA concentration the natural gene of AGA-specific tRNA and the artificial gene of AGG-specific tRNA were cloned in plasmid under the control of p15A ori compatible with co1EI ori and used for maintaining the model gene. It was shown that the artificial AGG-specific tRNA gene produces a functionally active tRNA. A steep rise in the synthesis of polypeptide encoded by the model template containing rare codons was demonstrated when the genes of tRNAs recognizing these codons were propagated in the multicopy plasmid. It was shown that AGA-specific tRNA efficiently translates both AGA and AGG codons while AGG-specific tRNA - only AGG codons.

Arginine↗
PubMed2004

[Correlation between mannose-binding lectin gene codon 54 polymorphism and susceptibility of Kawasaki disease].

OBJECTIVE: Human mannose-binding lectin (MBL) is a C-type serum lectin synthesized by the liver as an acute-phase protein. MBL can bind to glycoproteins terminated with mannose and N-acetylglucosamine present in the cell walls on a variety of microorganisms. Therefore, MBL appears to play an important role in the immune system. Low levels of MBL in human have been associated with a susceptibility to recurrent infections. MBL deficiency and low serum MBL levels are strongly associated with the presence of three point mutations at codon 52, 54 and 57 of exon 1 in the human MBL gene, and in Chinese population, the codon-54 mutation occurs at a frequency of 0.11 - 0.17. The data suggested that MBL insufficiency might also predispose to the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The possibility that Kawasaki disease (KD) is an infectious disease has been discussed and investigated for decades, in light of the implication that infections are involved in the pathogenesis of KD. It has been suggested that MBL insufficiency might predispose to the occurrence of KD. This study was aimed to investigate the genetic association of MBL codon-54 polymorphism in patients with KD, and to investigate possible associations with clinical manifestations of the disease. METHODS: There were 95 patients with KD and 160 healthy subjects in the study. The genotype of MBL gene 54 codon was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Clinical characteristics and biochemical examination were also performed. RESULTS: The genotype frequency of heterozygote (GGC/GAC) was significantly higher in KD group than that in healthy subjects (45.2% vs 25.0%, P < 0.01), and the allele frequency of GAC mutation was also higher in KD patients than that in control group (0.258 vs 0.138, P < 0.01). The variant allele (GAC) was markedly associated with KD (OR = 2.18, 95% CI = 1.38 approximately 3.44, P < 0.05). But there was no significant difference in the allele frequency of GAC between patients with and without coronary artery lesion (CAL) in KD cases (0.281 vs 0.246, P > 0.05). In addition, in cases of KD, more patients carrying the variant allele (GAC) had episodes of upper respiratory or gastrointestinal infections prior to the onset of KD than wild homozygotes (P < 0.01). CONCLUSION: The codon 54 polymorphism of MBL gene was associated with KD. It is possible that MBL gene codon 54 mutation might be related to the pathogenesis of KD.

Child↗
PubMedDate not supplied

[Protein environment of the sense codon of the template in the A site of the human ribosome as inferred from crosslinking to oligoribonucleotide derivatives].

The protein environment of each nucleotide of the template codon located in the A site of the human ribosome was studied with UUCUCAA and UUUGUU derivatives containing a Phe codon (UUC and UUU, respectively) and a perfluoroarylazido group at U4, U5, or U6. The analogs were positioned in the ribosome with the use of tRNA(Phe), which is cognate to the UUC or UUU codon and directs it to the P site, bringing a modified codon in the A site with a modified nucleotide occupying position +4, +5, or +6 relative to the first nucleotide of the P-site codon. On irradiation of ribosome complexes with tRNA(Phe) and mRNA analogs with mild UV light, the analogs crosslinked predominantly to the 40S subunit, modifying the proteins to a greater extent than the rRNA. The 18S rRNA nucleotides crosslinking to the analogs were identified previously. Of the small-subunit proteins, S3 and S15 were the major targets of modification in all cases. The former was modified both in ternary complexes and in the absence of tRNA, and the latter, only in ternary complexes. The extent of crosslinking of mRNA analogs to S15 decreased when the modified nucleotide was shifted from position +4 to position +6. The results were collated with the data on ribosomal proteins located at the decoding site of the 70S ribosome, and conclusion was made that the protein environment of the A-site codon strikingly differs between bacterial and eukaryotic ribosomes.

Codon↗
PubMed2005

A polymorphism at codon 133 of the tumor suppressor RASSF1A is associated with tumorous alteration of the breast.

The tumor suppressor gene RASSF1A is inactivated or mutated in different tumor entities including breast cancer. The frequency of the genomic variants of RASSF1A in patients with breast tumors has not been evaluated. We studied the association between ten nucleotide polymorphisms of RASSF1A and the risk of breast cancer in 178 cases with tumorous alterations of mammary tissue (including 141 carcinomas and 37 fibroadenomas) and 70 controls by SSCP and sequencing. Polymorphisms of RASSF1A were found at codon 28 and codon 133. The distribution of polymorphisms at codon 28 showed no significant difference between the patient groups: 5 of 178 (2.8%) in patients with tumorous alterations and 2 of 70 (2.9%) in control patients. However, the Gright curved arrow T polymorphism (GCTright curved arrow TCT; Alaright curved arrow Ser) at codon 133, which alters the microtubule association and stabilization domain of RASSF1A, exhibited a different genotype distribution: 29 out of 141 (20.6%) patients with breast carcinoma and 9 out of 37 (24.3%) patients with fibroadenoma harbored mutant T-alleles. However, only in 2 out of 70 (2.9%) controls, the mutant T-allele was detected and therefore the frequency was significantly diminished compared to tumorous alterations (Fisher's exact test: carcinomas vs. controls, p = 0.0003; fibroadenoma vs. controls, p = 0.001). From five probands with homozygous TT-genotype at codon 133, three were diagnosed with carcinomas and two with fibroadenomas. Our data indicate that the mutant T-allele of RASSF1A at codon 133 is correlated with an increased number of breast tumors.

Adult↗
PubMed1992

Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy.

A generalized deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT) is the inborn error in gyrate atrophy (GA), an autosomal recessive degenerative disease of the retina and choroid of the eye. Mutations in the OAT gene show a high degree of molecular heterogeneity in GA, reflecting the genetic heterogeneity in this disease. Using the combined techniques of PCR, denaturing gradient gel electrophoresis, and direct sequencing, we have identified three nonsense-codon mutations and one nonsense codon-generating mutation of the OAT gene in GA pedigrees. Three of them are single-base substitutions, and one is a 2-bp deletion resulting in a reading frameshift. A nonsense codon created at position 79 (TGA) by a frameshift and nonsense mutations at codons 209 (TAT----TAA) and 299 (TAC----TAG) result in abnormally low levels of OAT mRNA in the patient's skin fibroblasts. A nonsense mutation at codon 426 (CGA----TGA) in the last exon, however, has little effect on the mRNA level. Thus, the mRNA level can be reduced by nonsense-codon mutations, but the position of the mutation may be important, with earlier premature-translation termination having a greater effect than a later mutation.

Adult↗
PubMed2006

Prevalence and impact of HIV-1 protease codon 33 mutations and polymorphisms in treatment-naive and treatment-experienced patients.

BACKGROUND: HIV-1 protease gene mutations at codon 33 have been associated with resistance to some but not all protease inhibitors (PIs). Little is known about the difference in prevalence of codon 33 mutations and polymorphisms between treatment-naive and treatment-experienced patients, and the effect of codon 33F on PI phenotypic resistance patterns. METHODS: Baseline genotypes (TRUGENE) from 772 patients participating in two different randomized clinical trials [504 antiretroviral treatment-naive patients and 268 antiretroviral treatment-experienced patients] were evaluated for the presence of protease codon 33 mutations and polymorphisms. Baseline phenotypes (Antivirogram), including fold-change in resistance for 16 antiretroviral drugs, were available for the 268 treatment-experienced patients. Multivariate linear regression models were used to determine factors associated with phenotypic fold-change for PIs. RESULTS: The prevalence of codon 33 mutations and polymorphisms was 5.2% in the naive cohort (0.2% 33F, 2.5% 33V, 2.5% 331) and 34.7% in the experienced cohort (30.2% 33F, 1.5% 33V, 3.0% 331). In the antiretroviral-experienced cohort (mean = 4.2 prior PIs, 10.6 prior antiretroviral drugs overall), a model adjusting for the presence of specific major protease and multi-PI resistance conferring mutations, the number of other minor PI mutations, prior PI drug exposure (current, prior only, never), and HIV transmission risk factor was used to estimate the phenotypic fold-change in resistance for those with and without mutation 33F. Those with 33F had a significantly higher fold-change for amprenavir (33 vs 19, P<0.0001), ritonavir (162 vs 82, P<0.0001), lopinavir (49 vs 38, P=0.04), and saquinavir (47 vs 41, P=0.02). The presence of the 33F was not a significant predictor of fold change in susceptibility for indinavir or nelfinavir. CONCLUSIONS: At protease codon 33, the prevalences of polymorphisms 33V and 331 were similar for PI-naive and PI-experienced patients (<3.0%), but the prevalence of 33F was significantly different (0.2% versus 30.2%). In the treatment-experienced cohort, the differences in phenotypic fold-change for amprenavir, lopinavir, saquinavir, and ritonavir between those with and without 33F persist after adjustment for the presence of other major PI mutations and PI drug exposure history. Given the availability of newer PIs that may select for 33F, monitoring for the presence of this mutation should be ongoing for both treatment-naive and treatment-experienced patients.

Adult↗
PubMed1991

Specific degenerate codons enhanced selective expression of human parathyroid hormone in Escherichia coli.

Specific degenerate codons in the amino-terminal region of a synthetic human parathyroid hormone (PTH) gene exerted dramatic effects on both products and yield of expression of this 84-amino acid polypeptide in Escherichia coli. With adenine-rich degenerate codons constituting the PTH-(1-5) region, intact PTH has been expressed as the only PTH product at 6.5 mg/liter. In contrast, with guanine-rich degenerate codons, the predominent product was analogue PTH-(8-84). Use of cytosine- or thymine-rich degenerate codons generated only a small amount of immunoreactive product (0.2 mg/l). With the amino terminal region reconstituted with adenine-rich degenerate codons, the mid and carboxyl regions of the synthetic gene were also reconstructed to imitate the E. coli-favored codon degeneracy. Expression yielded the intact PTH at 20 mg/liter. Gel electrophoresis and Western blots, with antibodies specific to the amino or carboxyl terminus of PTH, indicated only a single PTH-related polypeptide, with the same mobility as a synthetic intact PTH sample. Amino acid sequencing, composition analysis, mass spectrometry, and the adenylate cyclase bioassays confirmed the purified product as the processed intact PTH.

Amino Acid Sequence↗
PubMed1989

Single base mutation in the type III procollagen gene that converts the codon for glycine 883 to aspartate in a mild variant of Ehlers-Danlos syndrome IV.

Experiments were carried out to test the hypothesis that a 19-year-old proband with a mild variant of Ehlers-Danlos syndrome type IV had a mutation in the gene for type III procollagen. cDNA and genomic DNA were analyzed by using the polymerase chain reaction and cloning of the products into M13 filamentous phage. A mutation was found that converted the codon for glycine 883 of the triple-helical domain in one allele for type III procollagen to a codon for aspartate. The polymerase chain reaction introduced a few artifactual single base substitutions. Also, it was difficult to distinguish copies from the two alleles in many of the M13 clones. Therefore, several different strategies and analyses of about 50,000 nucleotide sequences in a series of clones were used to demonstrate that the mutation in the codon for glycine 883 was the only mutation in coding sequences for the triple-helical domain of type III procollagen that could have contributed to the phenotype. The same mutation in the codon for glycine 883 in one allele for type III procollagen was found in the proband's 52-year-old father who also had a mild variant of Ehlers-Danlos syndrome type IV. The type III procollagen synthesized by the proband's fibroblasts was analyzed by polyacrylamide gel electrophoresis. Less type III procollagen was secreted by the proband's fibroblasts than by control fibroblasts. Also, the thermal stability of the type III procollagen synthesized by the proband's fibroblasts was lower than the thermal stability of normal type III procollagen as assayed by brief protease digestion. The results, therefore, demonstrated that the single base mutation that converted the codon of glycine 883 to a codon for aspartate destabilized the entire triple helix of type III procollagen and probably accounted for the mild phenotype of Ehlers-Danlos syndrome type IV seen in the proband and her father.

Adult↗
PubMedDate not supplied

[A stereochemical model of codon-anticodon interactions, in which bases bind via water bridges].

Analysis of available experimental data has allowed us to conclude that upon codon-anticodon interaction there is a functional asymmetry between the third nucleotide of the codon and the first nucleotide of the anticodon. We suggest that this phenomenon would be due to the differential codon and anticodon conformation mobilities, which are somehow restricted. Two postulates are proposed to restrict these mobilities respectively: (1) In the codon-anticodon complex the codon is in the fixed A-RNA conformation, and the rearrangement of the sugar-phosphate backbone, that is necessary for any wobble-pair formation occurs only in the anticodon. (2) This rearrangement does not alter the specific system of contacts between the universal uridine and other nucleotides in the anticodon loop, observed in tRNA crystals. Stereochemical analysis revealed that these restrictions make the construction of any Crick's wobble-pair sterically impossible. To resolve this contradiction we propose that two bases in the third position of the codon-anticodon complex can mate not only according to the Crick's scheme, but also with the help of water bridges. Consequently, besides the standard pairs, the following pairs become permitted: UG, UI, UU, CU, GU and AI (it should be noted that GU and AI are weaker that the other ones). All other pairs appear sterically impossible. These conclusions are in good agreement with the literature date.

Anticodon↗
PubMed1979

Relative efficiency of anticodons in reading the valine codons during protein synthesis in vitro.

Using a protein synthesizing in vitro system programmed with MS 2-RNA, the relative efficiency (in the presence of each other) of valine tRNAs with the anticodons U*AC (U* represents 5-oxyacetic acid uridine monophosphate), GAC, and IAC to read the valine codons was investigated. An anticodon which can read all three positions of the codon according to the rules of Watson-Crick base-pairing and the wobble hypothesis is an order of magnitude more efficient than an anticodon which misreads the codon by reading only the first two positions and presumably disregards the third nucleotide of the codon. There are two seeming exceptions to this behavior: the anticodon U*AC reads the codon GUU quite efficiently and IAC is as effective as U*AC in reading the codon GUG. The significance of these exceptions is evaluated with respect to the organization and evolution of the genetic code.

Anticodon↗
PubMed1994

HIV-1 syncytium-inducing phenotype, virus burden, codon 215 reverse transcriptase mutation and CD4 cell decline in zidovudine-treated patients.

The variable rate of disease progression in HIV-1-infected patients treated with zidovudine may be related to certain viral characteristics, such as, antiviral drug resistance, virus burden, and viral syncytium-inducing (SI) capacity. Thirty-two HIV-1-infected patients treated with zidovudine (mean of 34 months) were studied to determine the relationship of SI phenotype and the codon 215 pol gene mutation (a marker of zidovudine resistance) to virus burden and CD4 cell decline. Patients with SI strains and the codon 215 mutation in their proviral DNA had a 54% decline in CD4 cells and a virus burden of 21,480 proviral DNA copies/10(6) CD4 cells. In contrast, patients with non-SI (NSI) strains and wild-type at codon 215 had a 10% increase in CD4 cells and had a viral burden 1/46 that of patients with SI and the 215 mutation. Among patients with NSI strains, changes in CD4 cells depended on the presence of the codon 215 mutation (-160 CD4 cells/microliters), compared with those wild-type at codon 215 (+28 CD4 cells/microliters) (p < 0.01). There was a concordant rise in virus burden between proviral DNA and plasma HIV RNA depending on HIV phenotype and genotype. Using multiple linear regression, SI phenotype and the codon 215 mutation were found to independently predict CD4 cell decline and increased virus burden in zidovudine-treated patients.

CD4-Positive T-Lymphocytes↗
PubMed1994

Dinucleotide frequencies and codon usage in jawless and cartilaginous fishes.

Dinucleotide frequencies and codon usage in terms of strong-weak codon choices were examined in gene coding regions of 5 jawless and cartilaginous fish species. These dinucleotide frequencies were then compared to gene-coding regions from a vertebrate and an invertebrate species. These primitive vertebrate fishes exhibited species specificity in the hierarchy of dinucleotide frequencies. The most frequently occurring dinucleotide varied among coding regions of jawless and cartilaginous fishes, but it always contained G. Of the 16 dinucleotides, TA had the lowest frequency of occurrence in all species, and it had considerably lower frequencies in jawless fish genes than in cartilaginous fish genes. Dinucleotide frequency analysis suggested CpG conversion to TG in ray genes. Strong-weak codon usage analysis indicated that all 5 fish species used strong-weak-strong bonding codons most frequently; furthermore, each species used any-weak-strong codons in greater than expected levels. Gene coding regions from all 5 species exhibited a bias toward strong bonding nucleotides at codon position 3, with the greatest bias in sea lamprey genes. This bias may reflect the overall G+C content of localized regions of chromosomal DNA in which these genes reside.

Animals↗
PubMed1999

p53 codon 72 polymorphism in Taiwanese lung cancer patients: association with lung cancer susceptibility and prognosis.

An association between the BstUI (Pro/Pro) genotype of the p53 codon 72 polymorphism and lung cancer has been reported previously (X. Jin et al., Carcinogenesis (Lond.), 16: 2205-2208, 1995). However, the genotype distribution of p53 codon 72 polymorphism as well as the association of this polymorphism with lung cancer risk and prognosis remain undefined in the Taiwanese population. Therefore, we investigated the genotype distribution of p53 codon 72 polymorphism in 194 lung cancer patients and 152 noncancer controls. The genotype frequencies in Taiwanese noncancer controls were 0.56 (Arg) and 0.44 (Pro). Chi2 analysis indicated significant differences in genotype distribution of p53 from other reports in Swedish (P < 0.001), Spanish (P < 0.001), Caucasians in the United States (P = 0.002), and African-Americans (P = 0.027). In addition, our data suggest that the Pro allele of the p53 codon 72 polymorphism increased the risk of lung cancer among female Taiwanese. The female patients with genotype Pro/Pro showed a significantly increased odds ratio (3.14; confidence interval, 1.48-6.64; P = 0.003) of having lung adenocarcinoma, compared with normal controls with the other genotypes. Patients with the Pro/Pro genotype had an odds ratio of 2.63 (confidence interval, 1.22-5.68; P = 0.01) higher than those with the other genotypes to be diagnosed with lung cancer at the early ages. We further investigated the association of p53 codon 72 polymorphism with prognosis in 133 lung cancer patients. Patients with the Pro/Pro genotype tended to have poorer prognosis than those with the Arg/Pro genotype (P = 0.05, by the log-rank test). Our data suggested that p53 codon 72 polymorphism may play a role in cancer susceptibility and prognosis in specific classes of lung cancer patients in Taiwan.

Adenocarcinoma↗
PubMed2026

Molecular Determinants and Therapeutic Targeting of Stop Codon Readthrough in Eukaryotic Translation.

Accurate translation termination is essential for proteome integrity and in eukaryotes is primarily governed by the release factors eRF1 and eRF3, which ensure precise recognition of stop codons and efficient release of nascent polypeptides. However, proteome integrity is challenged by mutations that generate premature termination codons (PTCs), leading to truncated, nonfunctional proteins and degradation of the aberrant transcript via nonsense-mediated mRNA decay (NMD). Collectively, these events account for &#x223c;1800 human genetic diseases. Translational readthrough, the process by which near-cognate tRNAs decode stop codons and allow ribosomes to continue elongation beyond the stop codon, represents a possibility to suppress PTCs and restore full-length protein synthesis. Initially discovered in viruses as a mechanism to expand coding capacity, readthrough is now recognized as a regulated feature of eukaryotic gene expression influenced by both cis-acting sequence elements and trans-acting factors. Recent evidence highlights the remarkable context dependence of readthrough, revealing variation across transcripts, tissues, and developmental stages. In this review, we examine the molecular determinants that define stop codon recognition and readthrough efficiency, with particular emphasis on nucleotide context. We further discuss the mechanisms and binding sites of small molecules that promote PTC readthrough, and summarize the clinical development landscape of readthrough-inducing compounds for the treatment of diseases caused by nonsense mutations.

Humans↗