Abstract: |
Derangement of the p53 tumor suppressor gene has been implicated in the aetiology of a wide range of human neoplasias. We have previously determined that overexpression and mutation of the p53 gene in cultured metastatic melanomas is low (11%). However, two recent immunohistochemical studies have reported that >85% of malignant melanoma specimens overexpress mutated p53 protein. In an effort to resolve this contradiction in the published literature, we have re-evaluated a range of cultured and non-cultured melanocytic lesions for the occurrence of point mutations in the p53 gene using DNA- and RNA-dependent single strand conformation polymorphism (RNA-SSCP) and direct DNA sequencing of polymerase chain reaction (PCR) amplified DNA, and overexpression of the p53 protein using immunohistochemistry. We found point mutations in 25% (9 of 36) of cultured melanomas and 0% in 34 fresh melanoma biopsies; however, increased p53 expression was found in 42% of paraffin-embedded melanoma specimens and 7% of benign lesions. The low frequency of p53 point mutations and high frequency of p53 expression suggests that derangement of the p53 gene by point mutations is not a common perturbation in the majority of melanoma cells, and that overexpression of p53 in this tumour type is due to a mechanism other than point mutation. © 1994 Rapid Communications of Oxford Ltd. |
Keywords: |
immunohistochemistry; adult; clinical article; controlled study; human tissue; aged; aged, 80 and over; gene mutation; mutation; exons; polymerase chain reaction; melanoma; gene expression; melanocyte; tumor cells, cultured; protein p53; tumor suppressor gene; molecular sequence data; base sequence; malignant melanoma; dna, single-stranded; nucleic acid conformation; point mutation; rna, neoplasm; p53; genes, p53; paraffin embedding; middle age; human; male; female; priority journal; article; polymorphism (genetics); support, non-u.s. gov't; support, u.s. gov't, p.h.s.
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