Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Pigment Cell Melanoma Res. 2012 Jul;25(4):514-26. doi: 10.1111/j.1755-148X.2012.01010.x. Epub 2012 Jun 1.
Melanoma cell lines and normal human melanocytes (NHM) were assayed for p53-dependent G1 checkpoint response to ionizing radiation (IR)-induced DNA damage. Sixty-six percent of melanoma cell lines displayed a defective G1 checkpoint. Checkpoint function was correlated with sensitivity to IR with checkpoint-defective lines being radio-resistant. Microarray analysis identified 316 probes whose expression was correlated with G1 checkpoint function in melanoma lines (P≤0.007) including p53 transactivation targets CDKN1A, DDB2, and RRM2B. The 316 probe list predicted G1 checkpoint function of the melanoma lines with 86% accuracy using a binary analysis and 91% accuracy using a continuous analysis. When applied to microarray data from primary melanomas, the 316 probe list was prognostic of 4-yr distant metastasis-free survival. Thus, p53 function, radio-sensitivity, and metastatic spread may be estimated in melanomas from a signature of gene expression.
黑色素瘤细胞系和正常人黑色素细胞（NHM）被检测到对电离辐射（IR）诱导的 DNA 损伤的 p53 依赖性 G1 检查点反应。66%的黑色素瘤细胞系显示 G1 检查点缺陷。检查点功能与对 IR 的敏感性相关，具有检查点缺陷的细胞系具有抗辐射性。微阵列分析确定了 316 个探针，其表达与黑色素瘤细胞系中的 G1 检查点功能相关（P≤0.007），包括 p53 反式激活靶标 CDKN1A、DDB2 和 RRM2B。该 316 个探针列表使用二进制分析预测黑色素瘤细胞系的 G1 检查点功能的准确率为 86%，使用连续分析的准确率为 91%。当应用于原发性黑色素瘤的微阵列数据时，该 316 个探针列表可预测 4 年无远处转移的生存情况。因此，p53 功能、放射敏感性和转移扩散可以通过基因表达的特征来估计黑色素瘤。
