Genes involved in DNA repair and nitrosamine metabolism and those located on chromosome 14q32 are dysregulated in nasopharyngeal carcinoma
Genes involved in DNA repair and nitrosamine metabolism and those located on chromosome 14q32 are dysregulated in nasopharyngeal carcinoma
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DOI：
10.1158/1055-9965.epi-06-0455
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发表时间：
2006-11-01
影响因子：
3.8
通讯作者：
Hildesheim, Allan
中科院分区：
文献类型：
--
作者：
Dodd, Lori E.;Sengupta, Srikumar;Hildesheim, Allan
亚硝胺代谢、DNA修复和免疫应答基因的多态性与鼻咽癌（NPC）相关。研究表明染色体区域参与NPC。为了阐明鼻咽癌的病因，我们使用Affytechnic Human Genome U133 Plus 2.0 Array评估了31例鼻咽癌和10例正常鼻咽组织标本中的宿主基因表达模式。我们专注于五个先验生物学途径和染色体位置的基因。使用bootstrap方法测试这些预先指定的列表和总体内的差异表达率。在7.6%的探针组中观察到差异表达。在DNA修复（13.7%; P = 0.01）和亚硝胺代谢（17.5%; P = 0.04）途径中观察到差异表达率升高。DNA修复途径中差异表达的探针组一致过表达（93%），观察到PRKDC，PCNA和CHEK 1的强烈影响。亚硝胺代谢途径中差异表达的探针组始终低表达（100%），对NQ 01、CYP 2136和CYP 2 E1观察到强烈影响。在免疫/炎症途径中未观察到差异表达率增加的显著证据。染色体4p15.1- 4 q12的差异表达率显著升高（13.0%; P = 0.04）;过表达和低表达均明显（分别为38%和62%）。染色体14 q32的差异表达率升高（11.3%; P = 0.06），而基因低表达模式一致（100%; P < 0.0001）。当排除晚期肿瘤时，这些效应相似。我们的研究结果表明，亚硝胺激活和DNA修复是重要的NPC。染色体14 q32上表达的一致下调表明该区域的杂合性丢失。
Polymorphisms in nitrosamine metabolism, DNA repair, and immune response genes have been associated with nasopharyngeal carcinoma (NPC). Studies have suggested chromosomal regions involved in NPC. To shed light on NPC etiology, we evaluated host gene expression patterns in 31 NPC and 10 normal nasopharyngeal tissue specimens using the Affymetrix Human Genome U133 Plus 2.0 Array. We focused on genes in five a priori biological pathways and chromosomal locations. Rates of differential expression within these prespecified lists and overall were tested using a bootstrap method. Differential expression was observed for 7.6% of probe sets overall. Elevations in rate of differential expression were observed within the DNA repair (13.7%; P = 0.01) and nitrosamine metabolism (17.5%; P = 0.04) pathways. Differentially expressed probe sets within the DNA repair pathway were consistently overexpressed (93%), with strong effects observed for PRKDC, PCNA, and CHEK1. Differentially expressed probe sets within the nitrosamine metabolism pathway were consistently underexpressed (100%), with strong effects observed for NQ01, CYP2136, and CYP2E1. No significant evidence of increases in rate of differential expression was seen within the immune/inflammatory pathway. A significant elevation in rate of differential expression was noted for chromosome 4p15.1-4q12 (13.0%; P = 0.04); both overexpression and underexpression were evident (38% and 62%, respectively). An elevation in the rate of differential expression on chromosome 14q32 was observed (11.3%; P = 0.06) with a consistent pattern of gene underexpression (100%; P < 0.0001). These effects were similar when excluding late-stage tumors. Our results suggest that nitrosamine activation and DNA repair are important in NPC. The consistent down-regulation of expression on chromosome 14q32 suggests loss of heterozygosity in this region.