Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this present study, we report the mutation of the p53 gene in vivo in human primary carcinomas of cervix and cervical intraepithelial neoplasia (CIN). The association of the HPV subtypes with the tumors was determined by multiplex primer polymerase chain reaction (PCR) amplification. The mutation of the p53 gene was detected using PCR amplification of the p53 exons followed by SSCP (single strand conformation polymorphism) and DNA sequencing analysis. The p53 mutation was detected in two out of two HPV-33 positive carcinomas but was absent in the HPV-16/-18 positive carcinomas (0 out of 8 cases). The p53 mutation was also detected in one out of four HPV-negative cervical carcinomas. No mutation of the p53 gene was detected in the CIN specimens (0 out of 7 cases). The two mutations in the HPV-33 associated cervical carcinoma were detected at codon 273 (CGT to TGT; arginine to cysteine) and intron 5 (24 base pair downstream of the 3' end of exon 5). The p53 mutation at codon 273 has been previously reported in one of the HPV-negative cervical carcinoma cell line (C33A). Our results indicate that mutation of the p53 gene is not a common event in human cervical cancers (3/14), and may be related to the infection of HPV-16/18 in the tumor. However, mutation of the p53 gene was detected in cervical carcinomas associated with HPV-33 and may be an important genetic event in this subgroup of carcinomas.
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PMID:Presence of p53 mutation in human cervical carcinomas associated with HPV-33 infection. 136 12

Thyroid neoplasms show a wide variety of lesions varying from slowly growing differentiated adenocarcinomas to rapidly proliferating undifferentiated carcinomas. There has been some histopathological evidence that the undifferentiated thyroid carcinomas are derived from differentiated carcinomas. Moreover, it is suspected that some genetic events might be associated with such changes. In the present study, mutations in the p53 gene were investigated by direct sequencing analysis after polymerase chain reaction amplification of exons 5 to 8, using paraffin-embedded primary tumors and cultured cells. No mutations in exons 5 to 8 were detected in 10 differentiated papillary adenocarcinomas, whereas 6 of 7 undifferentiated carcinomas were found to carry base substitution mutations. Sequencing analysis confirmed mutations at codons 135 (TGC----TGT), 141 (CCC----CCT), 178 (CAC----GAC), 213 (CGA----TGA), 248 (CGG----CAG, CGG----TGG), and 273 (CGT----TGT). The spectrum of mutations (G:C to A:T transitions in 7 of 8) might be a specific feature of the spontaneous cancers. The results strongly suggest that, in human thyroid glands, p53 mutations play a crucial role in the progression of differentiated carcinomas to undifferentiated ones.
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PMID:Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland. 173

Genomic DNA was extracted from archival pathology specimens comprising 10 squamous and 14 adenocarcinomas, including 7 with Barrett's epithelium adjacent to tumor, and corresponding normal esophagus from the resection margin. The polymerase chain reaction was used to amplify selected exons of p53 which were analyzed for mutations using single-strand conformation polymorphism analysis. Mutations were localized to exon 8 for 1 adenocarcinoma and to exon 5 for 1 squamous tumor and 4 of 7 Barrett's specimens. Sequencing confirmed mutations at codons 273 (CGT----CAT; adenocarcinoma) and 176 (TGC----TTC; squamous) and in Barrett's epithelium at codons 152 (CCG----CTG), 155 (ACC----GCC) and 175 (CGC----CAC). Specimens of Barrett's epithelium from separate sites had identical p53 mutations suggesting a clonal origin. Cancers arising in mutant epithelium did not have mutations corresponding to those found in the Barrett's specimens suggesting that other events are required for tumorigenesis.
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PMID:p53 gene mutations in Barrett's epithelium and esophageal cancer. 186 73

We investigated the frequency of p53 mutations in 47 pediatric brain tumors of various histologic subtypes that were collected over a period of 5 years. The specimens included 15 primitive neuroectodermal tumors (PNETs), 17 low grade astrocytomas, one anaplastic astrocytoma, three glioblastomas (GBMs), one mixed glial tumor, eight ependymomas, one choroid plexus carcinoma, and one gangliocytoma/ganglioneuroma. Mutations were identified by single strand conformation polymorphism analysis of exons 4-8 and verified by sequencing. Mutations were present in 2 of 3 cases of GBM, but not in 17 low grade astrocytomas (P = 0.02, Fisher's exact test). One GBM demonstrated a germline GGC to AGC transition (gly to ser) at codon 245 with loss of the wild-type allele. A second GBM contained a CGG to TGG transition (arg to trp) at codon 248, also with loss of the wild-type allele, but normal tissue was not available for comparison. In addition, one of 15 PNETs retained heterozygosity but demonstrated a somatic CGT to TGT transition (arg to cys) at codon 273. p53 mutations were absent in other histologic subtypes and in two cases with multiple primary cancers. These data are consistent with earlier findings that p53 mutations are rare in PNETs, which are primarily pediatric tumors. In contrast to adult gliomas, p53 mutations in pediatric gliomas appear restricted to the GBMs. The lack of p53 mutations in pediatric low grade astrocytomas suggests not only histological differences, but also a different molecular pathogenesis in adult and pediatric patients.
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PMID:p53 gene mutations in pediatric brain tumors. 756 4

Overexpression and point mutation of the p53 protein/gene was investigated in a series of chondrosarcoma by an immunohistochemical approach, and direct sequencing of the genomic DNA, respectively. In 2 of the 16 cases studied, both of which were high grade chondrosarcomas (grade III), immunodetectable p53 was identified. Histologically, one was ordinary type and the other a clear cell variant. However, no positivity was observed in the other cases including nine of low grade, ordinary type, three of low grade, clear cell type, and two of extraskeletal myxoid chondrosarcoma. Direct sequencing, following polymerase chain reaction amplification of exons 5-9 of the p53 gene in 14 cases, in which fresh materials were available, successfully demonstrated base substitution mutations in only two cases with detectable p53 overexpression on immunohistochemistry. Their details were GTC (valine) to TTC (phenylalanine) at codon 157 in exon 5, and CGT (arginine) to CAT (histidine) at codon 273 in exon 8. No mutation was detected in the other 12 cases which were negative for p53 immunostaining. These findings strongly suggest that p53 mutation plays a crucial role in the biologically aggressive subtype, and possibly in the process of tumor progression in human chondrosarcoma.
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PMID:Possible association of p53 overexpression and mutation with high-grade chondrosarcoma. 811 3

DNA from tumor tissue and peripheral blood lymphocytes of primary breast cancer patients was screened for the presence of p53 mutations. In DNA from one tumor we found that the histidine codon 193 (CAT) was somatically converted to arginine (CGT). This amino acid residue is highly conserved in many species, thus suggesting that such mutation plays an important role in the loss of wt-p53 function.
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PMID:A novel p53 mutant in human breast cancer revealed by multiple SSCP analysis. 818 56

We have investigated the frequency of p53 gene mutations in Ewing's sarcoma (ES) and neuroblastoma (NB) by using polymerase chain reaction-single strand conformation polymorphism analysis for genomic DNA or complementary DNA generated from total RNA. Mutations of the p53 gene were found in six of seven ES cell lines: a missense mutation of TGC (Cys)-->TAC (Try) at codon 141 in one, a missense mutation of CGT (Arg)-->TGT (Cys) at codon 273 in one, a missense mutation of TGC (Cys)-->TTC (Phe) at codon 176 in three, and one base deletion of CGC-->CG at codon 283 in one. Further analysis of 14 ES and related primary tumors showed mutations of the p53 gene in only two: one base insertion of CCG-->CCCG at codon 152 in one and a missense mutation of GGC (Gly)-->GTC (Val) at codon 154 in the other. Both of the two tumors were obtained from patients with an advanced stage disease. Three of the eight ESs with mutations of the p53 gene showed the same missense mutation at codon 176, suggesting the mutational hot spot of the p53 gene in ESs. In contrast to ES, none of 6 NB cell lines or 48 NB tumors including advanced-stage ones with or without N-myc amplification showed any aberration of the p53 gene. Our findings suggest that mutations of the p53 gene in ES might represent late genetic events related to tumor progression, and that aberrations of the p53 gene might not be involved in the development or the progression of NB.
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PMID:Mutations of the p53 gene are involved in Ewing's sarcomas but not in neuroblastomas. 822 63

Human papillomavirus (HPV) infection is clearly associated with cervical carcinomas, yet it is also true that there are cervical carcinomas in which HPV DNA is absent. We examined eight established cell lines derived from cervical carcinomas for the presence of mutations of the p53 antioncogene in relation to the presence of HPV DNA sequences. Of these eight cell lines, seven were positive for HPV DNA and the remaining one was negative for HPV DNA. Single-strand conformation polymorphism analyses revealed a point mutation of the p53 gene in the cell line in which HPV DNA was absent. Sequencing analysis revealed a single-base mutation at codon 273 from CGT to CAT(Arg-->His) and immunocytochemical studies provided evidence that the p53 protein was overexpressed in this cell line. Our observations suggest that the loss of normal p53 gene function may be linked to the oncogenesis of cervical carcinoma.
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PMID:Correlation between HPV positivity and state of the p53 gene in cervical carcinoma cell lines. 838 Jul 85

A variety of neoplasms of the human nervous system were analyzed for the presence of mutations in the p53 tumor suppressor gene. DNA was extracted from frozen or formalin-fixed, paraffin-embedded material. Single-strand conformation polymorphism (SSCP) analysis for exons 5-8 was followed by direct DNA sequencing. Mutations leading to an amino acid change were found in three of 11 (27%) low-grade (World Health Organization (WHO) Grade II) astrocytomas. They were located in codon 183 (TCA-->TGA) of exon 5, codon 237 (ATG-->ATA) of exon 7, and codon 273 (CGT-->CAT) of exon 8. In one of these cases, the sequence indicated loss of the wild-type allele. Of 12 juvenile pilocytic astrocytomas (WHO Grade I), none contained a p53 mutation, suggesting a different molecular basis for this childhood neoplasm. Except for a mutation in one of seven (14%) meningeal hemangiopericytomas (codon 238; TGT-->TTT, Cys-->Phe), no mutations were observed in exons 5-8 of the p53 gene in any of the following tumors of the nervous system and its coverings: 13 schwannomas, 12 central neurocytomas, 22 meningiomas, 10 choroid plexus papillomas and carcinomas, and 30 neuroblastomas of the sympathetic nervous system. These and published data support the view that p53 mutations are frequently involved both in low-grade and progressive (anaplastic) astrocytomas, including glioblastomas multiforme. Oligodendrogliomas, medulloblastomas, meningiomas, and hemangiopericytomas rarely (< 15%) show p53 mutations in exons 5-8, whereas none of the remaining nervous system neoplasms revealed evidence of an involvement of the p53 gene in their development.
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PMID:Mutations of the p53 tumor suppressor gene in neoplasms of the human nervous system. 839 97

Non-familial human adrenocortical adenomas and carcinomas were screened for mutations in exons 5-8 of the p53 tumor suppressor gene by single-strand-conformation-polymorphism (SSCP) analysis, followed by direct sequencing of PCR-amplified DNA. Point mutations in codons 12, 13 and 61 in H-ras, K-ras and N-ras proto-oncogenes were similarly assessed by direct DNA sequencing. Three out of 15 primary adrenocortical carcinomas (20%) contained a mis-sense point mutation in the conserved regions (exons 5 and 8) of the p53 gene. Mutations were located in codon 157 (GTC-->TTC; Val-->Phe), codon 163 (TAC-->AAC; Tyr-->Asn), and codon 273 (CGT-->TGT; Arg-->Cys). The mutation in codon 157 was detected in the primary tumor as well as in brain and lymph-node metastases. Among 18 adrenocortical adenomas, there was only a single non-miscoding mutation in codon 295 (CCT-->CCC; Pro-->Pro). These data suggest that mutational inactivation of the p53 gene occurs in a minority (20%) of sporadic adrenocortical carcinomas and that these mutations constitute a late event in the multi-step process of malignant transformation. No ras mutations were detected in any of these tumors, suggesting that these genes are not involved in the development of tumors originating from the adrenal cortex.
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PMID:p53 mutations in sporadic adrenocortical tumors. 850 16


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