Mutation and expression of the p53 gene in human malignant melanoma.
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.
Laboratory of Mammalian Cell Transformation, Memorial Sloan Kettering Cancer Center, New York, NY 10021.
A P
AP
Albino
M J
MJ
Vidal
N S
NS
McNutt
C R
CR
Shea
V G
VG
Prieto
D M
DM
Nanus
J M
JM
Palmer
N K
NK
Hayward
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D004277:DNA, Single-Stranded / Q000032:analysis / Q000235:genetics; D005091:Exons; D005260:Female; D015870:Gene Expression; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016612:Paraffin Embedding; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012334:RNA, Neoplasm / Q000032:analysis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
D004277:DNA, Single-Stranded; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53