Albino A P, Vidal M J, McNutt N S, Shea C R, Prieto V G, Nanus D M, Palmer J M, Hayward N K
Laboratory of Mammalian Cell Transformation, Memorial Sloan Kettering Cancer Center, New York, NY 10021.
Melanoma Res. 1994 Feb;4(1):35-45. doi: 10.1097/00008390-199402000-00006.
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.
p53肿瘤抑制基因的紊乱与多种人类肿瘤的病因学有关。我们之前已经确定，在培养的转移性黑色素瘤中，p53基因的过表达和突变率较低（11%）。然而，最近两项免疫组织化学研究报告称，超过85%的恶性黑色素瘤标本中p53蛋白过表达且发生了突变。为了解决已发表文献中的这一矛盾，我们使用依赖DNA和RNA的单链构象多态性（RNA-SSCP）以及聚合酶链反应（PCR）扩增DNA的直接DNA测序，重新评估了一系列培养的和未培养的黑素细胞病变中p53基因点突变的发生情况，并使用免疫组织化学评估了p53蛋白的过表达情况。我们发现，25%（36个中有9个）的培养黑色素瘤存在点突变，34个新鲜黑色素瘤活检标本中未发现点突变；然而，在42%的石蜡包埋黑色素瘤标本和7%的良性病变中发现p53表达增加。p53点突变的低频率和p53表达的高频率表明，点突变导致的p53基因紊乱在大多数黑色素瘤细胞中并非常见的扰动，并且这种肿瘤类型中p53的过表达是由点突变以外的机制引起的。
