Mutation and expression of the p53 gene in human malignant melanoma

Albino, Anthony P.; Vidal, Marcos; McNutt, N. Scott; Shea, Christopher R.; Prieto, Víctor G.; Nanus, David M.; Palmer, Jane M.; Hayward, Nick

doi:10.1097/00008390-199402000-00006

Cited by 148 publications

(110 citation statements)

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“…These findings sharply contrast with the situation in human melanoma, in which p53 mutations are not commonly detected (Volkenandt et al, 1991;Castresana et al, 1993;Weiss et al, 1993;Lübbe et al, 1994;Albino et al, 1994;Florenes et al, 1994;Montano et al, 1994;Sparrow et al, 1995;Hartmann et al, 1996;Papp et al, 1996), with frequencies ranging from 0 to 6% in tumour samples (Castresana et al, 1993;Florenes et al, 1994;Lübbe et al, 1994;Papp et al, 1996). However, mutations in the N-ras gene have been shown to occur in at least 15% of melanomas (van Elsas et al, 1996) and occur more frequently in tumours from sun-exposed body sites compared with tumours from intermittently or unexposed sites, implicating sun exposure in the aetiology of these melanomas (van Elsas et al, 1996).…”

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confidence: 83%

p53 mutations in human cutaneous melanoma correlate with sun exposure but are not always involved in melanomagenesis

et al. 1999

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SummaryIn melanoma, the relationship between sun exposure and the origin of mutations in either the N-ras oncogene or the p53 tumoursuppressor gene is not as clear as in other types of skin cancer. We have previously shown that mutations in the N-ras gene occur more frequently in melanomas originating from sun-exposed body sites, indicating that these mutations are UV induced. To investigate whether sun exposure also affects p53 in melanoma, we analysed 81 melanoma specimens for mutations in the p53 gene. The mutation frequency is higher than thus far reported: 17 specimens (21%) harbour one or more p53 mutations. Strikingly, 17 out of 22 mutations in p53 are of the C:G to T:A or CC:GG to TT:AA transitional type, strongly suggesting an aetiology involving UV exposure. Interestingly, the p53 mutation frequency in metastases was much lower than in primary tumours. In the case of metastases, a role for sun exposure was indicated by the finding that the mutations are present exclusively in skin metastases and not in internal metastases. Together with a relatively frequent occurrence of silent third-base pair mutations in primary melanomas, this indicates that the p53 mutations, at least in these tumours, have not contributed to melanomagenesis and may have originated after establishment of the primary tumour.

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confidence: 83%

p53 mutations in human cutaneous melanoma correlate with sun exposure but are not always involved in melanomagenesis

et al. 1999

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“…Although p53 mutations are very rare in most melanomas, the melanoma cell line MeWo was reported to contain a p53 nonsense mutation at codon 341 (Albino et al 1994). According to our hypothesis, theoretically, if the function of p53 is completely impaired in MeWo cells, DFNA5 may not contribute to DNA damageinduced apoptosis in these cells.…”

Section: Discussionmentioning

confidence: 99%

The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage

Masuda

Futamura²,

Kamino³

et al. 2006

J Hum Genet

106

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The tumor suppressor p53 plays a crucial role in the cellular response to DNA damage by transcriptional activation of numerous downstream genes. Although a considerable number of p53 target genes have been reported, the precise mechanism of p53-regulated tumor suppression still remains to be elucidated. Here, we report a novel role of the DFNA5 gene in p53-mediated etoposide-induced cell death. The DFNA5 gene has been previously reported to be responsible for autosomal-dominant, nonsyndromic hearing impairment. The expression of the DFNA5 gene was strongly induced by exogenous and endogenous p53. The chromatin immunoprecipitation assay indicated that a potential p53-binding sequence is located in intron 1 of the DFNA5 gene. Furthermore, the reporter gene assay revealed that the sequence displays p53-dependent transcriptional activity. The ectopic expression of DFNA5 enhanced etoposide-induced cell death in the presence of p53; however, it was inhibited in the absence of p53. Finally, the expression of DFNA5 mRNA was remarkably induced by gammaray irradiation in the colon of p53(+/+) mice but not in that of p53(-/-) mice. These results suggest that DFNA5 plays a role in the p53-regulated cellular response to genotoxic stress probably by cooperating with p53.

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“…However, some melanomas which were immunopositive for p21 WAF1 contained foci within the tumour which were strongly immunopositive for p53 but which were p21 WAF1 negative. Because p21 WAF1 is mutated infrequently in melanoma (Vidal et al, 1995), it is likely that p53 was mutated in these clones, and suggests that when the TP53 gene becomes mutated (albeit at a low frequency) in cutaneous melanoma it occurs as a late event during melanoma progression (Castresana et al, 1993;Albino et al, 1994;Florenes et al, 1994;Lubbe et al, 1994;Montano et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of allelic losses in primary melanoma

et al. 1998

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Loss of genetic material, including loss of loci on chromosome arms 6q, 9p, and 10q, occurs frequently in cutaneous melanoma but infrequently in benign melanocytic nevi or other melanocytic lesions, suggesting that these genetic alterations are important in the development and progression of melanoma. To examine whether allelic loss is of prognostic importance in melanoma, disease-free survival was related to loss of heterozygosity on 6q, 9p and 10q in 83 individuals with sporadic primary cutaneous melanoma. Loss of chromosome arms 6q and 10q were each signi®cantly associated with a poorer clinical outcome (P=0.013 and P=0.001 respectively). In a subgroup of 41 subjects whose primary tumours were allelotyped, the fractional allelic loss (FAL) at 39 autosomal arms also signi®cantly correlated with disease-free survival (P=0.013), with an increase in FAL associated with a poorer outcome; this association remained signi®cant when controlled for tumour thickness (P=0.035). In addition, a greater proportion of cells were immunopositive for Ki67 antigen, p53 and p21 WAF1 protein in the primary melanomas than in the benign melanocytic nevi, however, only p53 overexpression was signi®cantly associated with improved survival (P=0.041).

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Mutation and expression of the p53 gene in human malignant melanoma

Cited by 148 publications

References 0 publications

p53 mutations in human cutaneous melanoma correlate with sun exposure but are not always involved in melanomagenesis

p53 mutations in human cutaneous melanoma correlate with sun exposure but are not always involved in melanomagenesis

The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage

Prognostic significance of allelic losses in primary melanoma

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