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)

Gorlin's syndrome, also known as multiple basal cell carcinoma syndrome, is a familial tumor condition with autosomal-dominant inheritance. Patients develop multiple basal cell carcinomas beginning in childhood. They also have a typical dysmorphic facies, skeletal malformations, and a particular type of epithelial cyst of the jaws. Recent evidence localizes a Gorlin's syndrome locus on chromosome 9 at band q31. Both tumors and malformations of the central nervous system occur with Gorlin's syndrome. Medulloblastoma is the primary brain tumor most frequently associated with this syndrome; over 40 such cases have been reported. However, only seven cases of meningioma associated with Gorlin's syndrome have been described. The authors report the case of a woman with Gorlin's syndrome whose mother and maternal grandfather also had the condition. The patient was found to have a medulloblastoma at 4 years of age and presented with a large bifrontal meningioma at 19 years of age. The meningioma was histologically malignant and had a complex karyotype with multiple translocations including a t(5;9) with the breakpoint on chromosome 9 located at 9q32. The constitutional karyotype of the mother was normal. No mutations of exons 5 to 9 of the p53 gene were detected using single-stranded conformational polymorphism analysis.
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PMID:Malignant meningioma in Gorlin's syndrome: cytogenetic and p53 gene analysis. Case report. 805 57

To determine the role of the p53 gene in the pathogenesis of basal cell carcinoma (BCC), we screened mutations of the gene in 11 cases of BCCs using the polymerase chain reaction (PCR) and single-stranded conformation polymorphism (SSCP). However, in all the coding exons of the gene analysed, no evidence suggesting the mutations were obtained. On the other hand, in 2 of 5 informative cases of our BCCs (40%) we found loss of heterozygosity (LOH) for loci on chromosome 9q31 which is linked to the Gorlin syndrome, that predisposes to BCC. Therefore, we suggest that a putative tumor suppressor gene on the region of 9q, but not p53 gene, plays a critical role in the pathogenesis of BCC, independent of race.
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PMID:Analysis of p53 gene mutations and loss of heterozygosity for loci on chromosome 9q in basal cell carcinoma. 818 55

Medulloblastoma (MB) is a primitive neuroectodermal tumour of the cerebellum whose pathogenesis is poorly understood. Previous studies suggest a role for loci on chromosomes 11p and 17p in the pathogenesis of MB. Evidence for another potential MB locus has recently emerged from studies on Gorlin syndrome (GS), an autosomal dominant syndrome with multiple basal cell carcinomas, epithelial jaw cysts, and skeletal anomalies. Since GS can be associated with MB, we examined sporadic (non-GS) cases of MB for evidence of loss of heterozygosity (LOH) on chromosome 9 where a putative GS locus has been localized to band q31. Nineteen paired blood and MB DNA specimens from 16 patients (11 primary tumours, two primary with recurrent tumours, one primary tumour and cell line, two cell lines) were studied by PCR analysis of microsatellites at D9S55 (9p12), D9S15 (9q13-q21.1), D9S127 (9q21.1-21.3), D9S12 (9q22.3), D9S58 (9q22.3-q31), D9S109 (9q31), D9S53 (9q31), GSN (9q33), D9S60 (9q33-q34), D9S65 (9q33-q34), ASS (9q34), D9S67 (9q34.3), TH (11p15.5), D11S490 (11q23.3), D17S261 (17p11.2-12), D17S520 (17p12), TP53 (17p13.1), D17S5 (17p13.3), D17S515 (17q22-qter), and by RFLP analysis at the WT-1 locus (11p13). Only two tumours had LOH on 9q. One was non-informative at D9S15, D9S65, and GSN but showed LOH at D9S127, D9S12, D9S58, D9S109, D9S53, D9S60, ASS, and D9S67. The other was uninterpretable at D9S65 and non-informative at D9S15, D9S58, D9S53, and D9S67 but exhibited LOH at D9S127, D9S12, D9S109, GSN, D9S60, and ASS. Both these cases were informative at D9S55 without LOH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microsatellite analysis of loss of heterozygosity on chromosomes 9q, 11p and 17p in medulloblastomas. 820 43

Basal cell carcinoma (BCC) of the skin represents a unique group of tumors strongly associated with exposure to UV light. Unlike squamous carcinoma of the skin, BCC is generally indolent, noninvasive, and rarely metastatic. To study the involvement of tumor suppressor genes in these neoplasms, we analyzed 36 BCCs for p53 mutations and a subset of these tumors for loss of chromosomes 17p and 9q. Sixty-nine % of sporadic BCCs had lost a 9q allele, with the common area of loss surrounding the putative gene for nevoid BCC or Gorlin's syndrome. Forty-four % (16 of 36) of BCCs had a mutated p53 allele, usually opposite pyrimidine tracts, which is consistent with UV-induced mutations. Surprisingly, only one tumor had lost a 17p allele, and in all BCCs only one p53 allele was inactivated. This is in direct contrast to other epithelial tumors, which usually progress by the inactivation of both p53 alleles.
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PMID:Progression of basal cell carcinoma through loss of chromosome 9q and inactivation of a single p53 allele. 826 48

Mutations in p53, a tumor suppressor gene, are one of the most common genetic lesions of human cancers. The relationship between p53 gene mutation and ultraviolet (UV) light has been demonstrated in skin cancers of sun-exposed sites. In this study, genomic DNA from 12 skin cancers was screened for mutations in exons 5 to 9 of this gene using the polymerase chain reaction--single strange configuration polymorphism (PCR-SSCP) analysis followed by DNA sequencing. DNA samples were obtained from 8 basal cell carcinomas (BCCs): 1 from an organoid nevus, 1 from a patient with basal cell nevus syndrome, 1 from a patient with xeroderma pigmentosum, and 1 from a recurrent and 4 from primary sporadic lesions on actinic damaged skin, and from 4 squamous cell carcinomas (SCCs): 1 from a burn scar, 1 from a patient with epidermodysplasia verruciformis, and 2 from actinic keratosis. Mutation of the p53 gene was detected in only 1 case of SCC which had arisen from actinic keratosis. The mutation occurred at codon 159 in exon 5 with a GCC to CCC base-pair substitution resulting in an amino acid change of alanine to proline. This mutation does not correspond to results of UV mutagenesis studies reported in the literature. Our findings imply that, although p53 gene mutation and UV exposure play an important role in the carcinogenesis of some skin cancers, they are not crucial, especially in skin cancers that develop from underlying skin disorders.
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PMID:p53 gene mutations in skin cancers with underlying disorders. 866 19

The expression of p53 protein was studied in odontogenic keratocysts (OKC, 11 solitary, 5 recurrent and 6 NBCCS cysts), radicular (RC, n = 5) and dentigerous (DC, n = 5) cysts, using a panel of antibodies to p53 (clone BP53-12, clone 1801 and polyclonal CM1) and a sensitive biotin-streptavidin method on paraffin embedded sections. Of the three antibodies tested, clone BP53-12 gave the most intense and consistent nuclear staining pattern. Clone 1801 and polyclonal CM1 stained only 38% and 71% OKC linings, respectively, but not RC and DC linings. However, BP53-12+ cells were detected in the epithelial linings of all cyst types. Quantification of BP53-12+ cells was performed by manual counting and by relating cell number to unit length of basement membrane as determined by TV image analysis. BP53-12+ cell counts in solitary OKC linings (25.5 +/- 11.0 cells/mmBM) were significantly greater than those in DC (9.3 +/- 4.9 cells/mmBM, P < 0.01) and RC (6.7 +/- 2.6 cells/mmBM, P < 0.01) linings. The epithelial distribution of positive cells in OKC was predominantly suprabasal, which also varied from that of DC and RC linings (P < 0.005). There were no detectable differences in BP53-12 reactivity between the different subtypes of OKC (i.e., solitary, recurrent and NBCCS-associated OKC; P > 0.1). When data for the NBCCS-related OKC group were excluded, there was a significant correlation (r = 0.55, P < 0.01) between p53 and Ki67 labelling. To detect the presence of p53 gene mutations, genomic DNA, extracted from paraffin sections of OKC (4 solitary, 2 recurrent and 4 NBCCS cysts), RC (n = 3) and normal oral mucosa (n = 1), was subjected to a combination of polymerase chain reaction and single-stranded conformation polymorphism (PCR-SSCP) analysis for exons 5-10 of the p53 gene. Exon 4 was not analysed because of compromised DNA quality. No abnormality in banding patterns was found and all samples gave results similar to DNA from known, sequenced, normal p53 gene controls. Absence of p53 mutations within exons 5-9 was confirmed by the direct sequencing of 2 fresh frozen OKC samples (1 solitary and 1 NBCCS cyst). These results suggest that overexpression of p53 protein in OKC epithelium, detected by immunocytochemistry, is not reflected by alteration of the p53 gene and presumably reflects overproduction and/or stabilisation of normal p53 protein.
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PMID:p53 expression in odontogenic keratocyst epithelium. 883 23

Mutation of the p53 tumour suppressor gene can produce a more stable protein that does not inhibit mitosis, accumulates in the nucleus and can then be detected immunohistochemically in many human tumours using antibody CM-1. The protein has also been detected in odontogenic keratocysts. Routinely processed material from 30 odontogenic keratocysts was immunostained with antibody CM-1. Ten were recurrences and five were associated with the basal-cell naevus syndrome (Gorlin-Goltz syndrome). p53 protein was found in 50% (15/30) of the odontogenic keratocysts, in 53.3% (8/15) of non-recurrent cysts, in 40% (4/10) of recurrent cysts and in 60% (3/5) of those associated with the basal-cell naevus syndrome. Staining was weak and speckled and limited to occasional basal and suprabasal cells. There was no statistically significant difference in staining between these groups and no correlation between expression and the presence of satellite cysts, basal-cell budding or islands of odontogenic epithelium. The low levels of expression may represent physiological expression of wild-type p53 protein rather than mutant or complexed p53 protein.
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PMID:p53 immunohistochemistry of odontogenic keratocysts in relation to recurrence, basal-cell budding and basal-cell naevus syndrome. 885 Jun 45

The following conclusions are derived from an epidemiological study. Reduced repair of ultraviolet (UV)-induced DNA damage contributes directly to basal cell carcinoma (BCC) in individuals with prior sunlight overexposure. A family history of BCC is a predictor of low DNA repair. Repair of UV-damaged DNA declines at a fixed rate of approximately 1% per annum in noncancerous controls. The DNA repair differences between young BCC cases and their controls disappear as they age. Hence, BCC, in terms of DNA repair, is a premature aging disease. The persistence of photochemical damage because of reduced repair results in point mutations in the p53 gene and allelic loss of the nevoid BCC gene (Gorlin's syndrome) located on chromosome 9q. The fact that environmental vulnerability is gender oriented implicates hormones in regulating DNA repair. Xeroderma pigmentosum appears to be a valid paradigm for the role of DNA repair in BCC in the general population.
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PMID:Epidemiology of ultraviolet-DNA repair capacity and human cancer. 925 82

Odontogenic keratocysts are occasionally (4-5%) associated with the nevoid basal cell carcinoma syndrome, a pleiotropic, autosomal disorder presenting a spectrum of developmental abnormalities and a predisposition for the development of different neoplasms. The aim of this study was to establish whether keratocysts showing clinically aggressive behavior associated with nevoid basal cell carcinoma syndrome reflect differences in cellular proliferation rate and/or in the expression of oncoproteins and tumor suppressor genes. For this reason, formalin-fixed paraffin-embedded sections of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome (16 cases) and sporadic odontogenic keratocysts (16 cases) were compared for expression of proliferating cell nuclear antigen (PCNA) and p53, bcl-2, and bcl-1 (cyclin D1) onco-proteins. Most of the epithelial lining of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome showed nuclear immunopositivity for p53 protein and overexpression of cyclin D1 with various degrees of staining intensity. All sporadic odontogenic keratocysts were negative for p53 and cyclin D1. The expressions of bcl-2 oncoprotein were found to be substantially similar between the two groups of lesions, with a cytoplasmic immunopositivity localized only in the resting reserve basal layer of the epithelium. PCNA expression showed no statistically significant difference between the two groups of lesions. In conclusion, the finding of cyclin D1 and p53 overexpression in odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome could be considered a hallmark of a mutated cellular phenotype, thus leading to the hypothesis that their aggressive clinical behavior could be due to a dysregulation of the expression of cyclin D1 and p53 proteins, involved in a check-point control of cellular proliferation.
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PMID:Expression of cell cycle and apoptosis-related proteins in sporadic odontogenic keratocysts and odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome. 1040 62

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by nevi, palmar and plantar pits, falx calcification, vertebrate anomalies and basal cell carcinomas. It is well known in NBCCS that gamma-irradiation to the skin induces basal cell carcinomas or causes an enlargement of the tumor size, although the details of the mechanism remain unknown. We have established lymphoblastoid cell lines from three NBCCS patients, and we present here the first evidence of abnormal cell cycle and apoptosis regulations. A novel mutation (single nucleotide deletion) in the coding region of the human patched gene, PTCH, was identified in two sibling patients, but no apparent abnormalities were detected in the gene of the remaining patient. Nevertheless, the three established cell lines showed similar features in the following analyses. Flow cytometric analyses revealed that the NBCCS-derived cells were accumulated in the G2M phase after gamma-irradiation, whereas normal cells showed cell cycle arrest both in the G0G1 and G2M phases. The fraction of apoptotic cells after gamma-irradiation was smaller in the NBCCS cells. The level of p27 expression markedly decreased after gamma-irradiation in the NBCCS cells, although the effects of the irradiation on the expression profiles for p53, p21 and Rb did not differ in normal and NBCCS cells. These findings may provide a clue to the molecular mechanisms of tumorigenesis in NBCCS.
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PMID:Gamma-irradiation deregulates cell cycle control and apoptosis in nevoid basal cell carcinoma syndrome-derived cells. 1066 53


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