Chang Kai-Ping, Hao Sheng-Po, Tsang Ngan-Ming, Chang Yu-Liang, Cheng Ming-Huei, Liu Chun-Ting, Lee Yun-Shien, Tsai Chia-Lung, Lee Ta-Jen, Wang Tzu-Hao, Tsai Chi-Neu
Department of Otolaryngology - Head and Neck Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
Oncol Rep. 2008 Jan;19(1):217-22.
Overexpression of the DNA methyltransferase 3B (DNMT3B) gene and its effect on carcinogenesis has been demonstrated for various types of cancer. Recently, three single nucleotide polymorphisms (SNPs) of the DNMT3B promoter region, C46359T (-149C>T), -283T>C, and -579G>T have also been reported to be stratification markers that can predict an individual's susceptibility to cancers. In this study, we analyzed expression of DNMT3B in nasopharyngeal carcinoma (NPC) specimens and did not find elevated levels of DNMT3B in tumors using cDNA microarray analysis and RT-PCR. Meanwhile, 259 NPC patients and 250 controls were genotyped for the above three SNPs using a MALDI-TOF based mini-sequencing method. For C46359T (-149C>T), only the T/T genotype was found to be present in both patient and control groups (100% frequency). The frequency of the genotypes, -283CC, -283CT and -283TT, amongst NPC patients versus controls was, respectively, 86.1% versus 84.0%, 13.5% versus 15.6%, and 0.4% versus 0.4% (P=0.589). The allele frequency, -597TT, -597GT and -597GG, for patients versus controls was, respectively, 87.3% versus 84.8%, 12.0% versus 15.2%, and 0.8% versus 0 (P=0.501). The distribution of SNPs among cancer patients either featuring or not featuring cervical metastasis also did not reveal any significant difference. In conclusion, our data indicate that neither overexpression of DNMT3B nor the presence of three DNMT3B SNPs are associated with NPC, which suggests that DNMT3B might not play a role in hypermethylation of many tumor suppressor genes during carcinogenesis of NPC.
DNA甲基转移酶3B（DNMT3B）基因的过表达及其对致癌作用的影响已在多种癌症类型中得到证实。最近，据报道，DNMT3B启动子区域的三个单核苷酸多态性（SNP），即C46359T（-149C>T）、-283T>C和-579G>T，是可以预测个体癌症易感性的分层标志物。在本研究中，我们分析了鼻咽癌（NPC）标本中DNMT3B的表达情况，通过cDNA微阵列分析和逆转录聚合酶链反应（RT-PCR）未发现肿瘤中DNMT3B水平升高。同时，使用基于基质辅助激光解吸电离飞行时间（MALDI-TOF）的微测序方法对259例NPC患者和250例对照进行了上述三个SNP的基因分型。对于C46359T（-149C>T），仅发现T/T基因型在患者组和对照组中均存在（频率为100%）。NPC患者与对照组中-283CC、-283CT和-283TT基因型的频率分别为86.1%对84.0%、13.5%对15.6%和0.4%对0.4%（P=0.589）。患者与对照组中-597TT、-597GT和-597GG等位基因频率分别为87.3%对84.8%、12.0%对15.2%和0.8%对0（P=0.501）。在有或没有颈部转移的癌症患者中，SNP的分布也未显示出任何显著差异。总之，我们的数据表明，DNMT3B的过表达和三个DNMT3B SNP的存在均与NPC无关，这表明DNMT3B在NPC致癌过程中可能不会在许多肿瘤抑制基因的高甲基化中起作用。
