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Updated: Aug 16, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Comprehensive analysis of the p53 status in mucosal and cutaneous melanomas
Christian Gwosdz1, Kathrin Scheckenbach, Oliver Lieven
1Department of Otorhinolaryngology/Head and Neck Surgery, Heinrich-Heine-University, Düsseldorf, Germany.
Abstract:
The abrogation of the function of the "gatekeeper of the genome", p53, is the most prevalent molecular alteration in solid human tumors. Regarding melanomas the involvement of p53 alterations is discussed controversially to date. In order to evaluate the status of p53 in detail, primary tumors and metastases of 63 sporadic cutaneous (CM) and mucosal (MuM) melanomas were examined by immunohistochemistry and sequence analysis of the entire coding region of the p53 transcript, i.e., exons 2 to 11. In addition, loss of heterozygosity (LOH) and loss of allele-specific transcription (LOT) were determined. Accumulation of the p53 protein occurred in most of the CM and MuM specimens (71% and 58%, respectively). In contrast, protein stabilizing p53 mutations were observed in 14% of the CM and no mutation was found in MuM specimens. Two of the aberrations located outside the core domain. LOH was detected in 22% CM and 58% MuM, and LOT in 25% of the CM specimens. The genotype distribution at the polymorphic p53 codon 72 in melanoma patients differed significantly from control subjects. The calculation of odds ratios (OR) and 95% confidence intervals (CI) indicated an increased risk for developing cutaneous melanomas in individuals carrying the Pro-coding allele. Altogether, aberrant p53 expression appears to be a common event in both CM and MuM.
Insights
Aberrant p53 expression is common in cutaneous melanoma (CM) and mucosal melanoma (MuM). p53 protein accumulation occurred in most cases, with mutations found in CM, suggesting p53
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The tumor suppressor gene p53, often called the "gatekeeper of the genome", is frequently altered in human cancers.
- The role of p53 alterations in melanoma, particularly cutaneous melanoma (CM) and mucosal melanoma (MuM), remains controversial.
Purpose of the Study:
- To comprehensively investigate the status of p53 in primary and metastatic CM and MuM.
- To analyze p53 mutations, loss of heterozygosity (LOH), and loss of allele-specific transcription (LOT).
Main Methods:
- Immunohistochemistry and sequence analysis of the entire p53 coding region (exons 2-11) in 63 CM and MuM samples.
- Determination of LOH and LOT for p53.
- Genotyping at the polymorphic p53 codon 72 and risk assessment using odds ratios (OR) and confidence intervals (CI).
Main Results:
- p53 protein accumulation was observed in 71% of CM and 58% of MuM.
- Mutations were found in 14% of CM, with two located outside the canonical core domain; no mutations were detected in MuM.
- LOH was detected in 22% of CM and 58% of MuM; LOT was found in 25% of CM.
- The p53 codon 72 genotype distribution differed significantly between melanoma patients and controls, with the Pro-coding allele associated with increased CM risk.
Conclusions:
- Aberrant p53 expression is a frequent event in both CM and MuM.
- p53 alterations, including mutations, LOH, and LOT, contribute to melanoma development.
- Specific p53 genotypes, like the Pro-coding allele at codon 72, may confer an increased risk for cutaneous melanoma.
