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题目:: Transcription profiling of human normal melanocytes and melamoma cell lines reveal defective cell cycle checkpoint functions in melanoma are associated with altered patterns of gene expression
ID:
状态:: 发布时间June 15, 2008 , 更新时间 May 2, 2014 , 提交时间 April 5, 2007,
物种:: Homo sapiens
摘要:: Defects in DNA damage responses may underlie genetic instability and malignant progression in melanoma. Cultures of normal human melanocytes (NHMs) and melanoma lines were analyzed to determine whether global patterns of gene expression could predict the efficacy of DNA damage cell cycle checkpoints that arrest growth and suppress genetic instability. NHMs displayed effective G1 and G2 checkpoint responses to ionizing radiation-induced DNA damage. A majority of melanoma cell lines (11/16) displayed significant quantitative defects in one or both checkpoints. Melanomas with B-RAF mutations as a class displayed a significant defect in DNA damage G2 checkpoint function. In contrast the epithelial-like subtype of melanomas with wildtype N-RAS and B-RAF alleles displayed an effective G2 checkpoint but a significant defect in G1 checkpoint function. RNA expression profiling revealed that melanoma lines with defects in the DNA damage G1 checkpoint displayed reduced expression of p53 transcriptional targets, such as CDKN1A and DDB2, and enhanced expression of proliferation-associated genes, such as CDC7 and GEMININ. A Bayesian analysis tool was more accurate than significance analysis of microarrays for predicting checkpoint function using a leave-one-out method. The results suggest that defects in DNA damage checkpoints may be recognized in melanomas through analysis of gene expression. Experiment Overall Design: Normal human melanocyte and melanoma cell lines w/wo mutations in B-raf or N-ras were treated with 1.5 Gy IR irridiartion for G1 and G2 checkpoint determination. RNA was isolated from exponentially growing cultures and applied for microarray hybridizaton with Agilent 44 K (G4112A) array.
实验种类:: transcription profiling by array
样本量:: 46
实验设计:
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数据号:: E-GEOD-7469, GSE7469
数据状态:: 无法自动分析，您可以尝试手动分析数据。

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