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| 1 | Identification of EGFR kinase domain mutations among lung cancer patients in China:implication for targeted cancer therapy显示文摘Lung cancer is one of the leading causes of death with one of the lowest survival rates. However, a subset of lung cancer patients who are of Asian origin and carry somatic mutations in epidermal growth factor receptor or EGFR have responded remarkable well to two tyrosine kinase inhibitors, gefitinib and erlotinib. While EGFR mutation profiles have been reported from Japan, South Korea, and Taiwan, there is no such report from mainland of China where the largest pool of patients reside. In this report, we identified ten somatic mutations from a total of 41 lung cancer patients in China. Among them, seven mutations were found in 17 adenocarcinomas. In contrast to previous reports, eight of these mutations are deletions in exon 19 and two of these deletions are homozygous. These results suggest that a large portion of Chinese adenocarcinoma patients could benefit from gefitinib or erlotinib. This unique mutation profile provides a rationale to develop the next generation of EGFR inhibitors more suitable for the Chinese population. | BaoMingQIN XiaoCHEN JingDeZHU DuanQingPEI | 2005 | Cell Research2005，15，3： | 66 |
| 2 | Methylation profiling of twenty four genes and the concordant methylation behaviours of nineteen genes that may contribute to hepatocellular carcinogenesis显示文摘To determine the possible role of the epigenetic mechanisms in carcinogenesis of the hepatocellular carcinoma,we methylation-profiled the promoter CpG islands of twenty four genes both in HCC tumors and the neighboring non-cancerous tissues of twenty eight patients using the methylation-specific PCR (MSP) method in conjunction with the DNA sequencing. In comparison with the normal liver tissues from the healthy donors, it was found that while remained unmethylated the ABL, CAV, EPO, GATA3, LKB 1, NEP, NFL, NIS and p27KIP1 genes, varying extents of the HCC specific hypermethylation were found associated with the ABO, AR, CSPG2, cyclin al, DBCCRl,GALR2, IRF7, MGMT, MT1A, MYOD1, OCT6, p57KIP2, p73, WT1 genes, and demethylation with the MAGEA1 gene, respectively. Judged by whether the hypermethylated occurred in HCC more frequently than in their neighboring normal tissues, the hypermethylation status of the AR, DBCCR1, IRF7, OCT6, and p73 genes was considered as the event specific to the late stage, while that the rest that lacked such a distinguished contrast, as the event specific to the early stage of HCC carcinogenesis. Among all the clinical pathological parameters tested for the association with, the hypermethylation of the cyclin al gene was more prevalent in the non-cirrhosis group (P=0.021) while the hypermethylated p 16INK4a gene was more common in the cirrhosis group (P=0.017). The concordant methylation behaviors of nineteen genes, including the four previously studied and their association with cirrhosis has been evaluated by the best subgroup selection method. The data presented in this report would enable us to shape our understanding of the mechanisms for the HCC specific loss of the epigenetic stability of the genome, as well as the strategy of developing the novel robust methylation based diagnostic and prognostic tools. | JIANYU HONGYuZHANG ZHENZHONGMA WEILU YIFEIWANG JINGDEZHU | 2003 | Cell Research2003，13，5： | 33 |
| 3 | The altered DNA methylation pattern and its implications in liver cancer显示文摘DNA methylation is the most intensively studied epigenetic phenomenon, disturbances of which result in changes ingene transcription, thus exerting drastic imparts onto biological behaviors of cancer. Both the global demethylation andthe local hypermethylation have been widely reported in all types of tumors, providing both challenges and opportunitiesfor a better understanding and eventually controlling of the malignance. However, we are still in the very early stage ofinformation accumulation concerning the tumor associated changes in DNA methylation pattern. A number of excellentrecent reviews have covered this issue in depth. Therefore, this review will summarize our recent data on DNA methy-lation profiling in cancers. Perspectives for the future direction in this dynamic and exciting field will also be given. | JingDeZHU | 2005 | Cell Research2005，15，4： | 17 |
| 4 | A novel protein-DNA interaction involved with the CpG dinucleotide at -30 upstream is linked to the DNA methylation mediated transcription silencing of the MAGE-A1 gene显示文摘To understand the DNA-methylation mediated gene silencing mechanisms, we analyzed in cell culture of the promoter function of the MAGE-A1 gene, which is frequently demethylated and over-expressed in human hepatocellular carcinoma. We have established the correlation of the DNA methylation of the promoter CpG island with expression status of this gene in a panel of the established liver cancer cell lines. The crucial CpG dinucleotide(s) within the minimal promoter subjected to the control mediated by DNA methylation with profound biological functions was also delineated.Furthermore, a novel sequence-specific DNA-protein interaction at the -30 CpG dinucleotide upstream of the gene was found having a vital part to play in the DNA methylation mediated transcription silencing of the MAGE-A1 gene. Our results would not only provide new insights into the DNA methylation mediated mechanisms over transcription of the MAGE-A1 gene, but also pave the way for further defining the cross-talk among DNA methylation, histone modification and chromatin remodeling in detail. | JieZHANG JianYU JunGU BaoMeiGAO YingJunZHAO PengWANG HongYuZHANG JingDeZHU | 2004 | Cell Research2004，14，4： | 3 |
| 5 | The ATF/CREB site is the key element for franscription of the human RNA methyransferase likel(RNMTL1)gene,a newly discovered 17p13.3 gene显示文摘The human RNA methyltransferase like i gene (RNMTL1) is one of thirteen newly discovered geneswithin a 116 Kb segment of the chromosome 17p13.3 that suffers from a high frequent loss of heterozygosityin human hepatocellular carcinoma in China[1-5]. To understand the molecular mechanisms underlyingtranscription control of the RNMTL1 gene in human cancers, we decline using of the conventional approachwhere the cis-elements bound by the known transcription factors are primary targets, and carried out thesystematic analyses to dissect the promoter structure and identify/characterize the key cis-elements thatare responsible for its strong expression in cell. The molecular approaches applied included 1, the primerextension for mapping of the transcription starts; 2, the transient transfection/reporter assays on a largenumber of deletion and site-specific mutants of the promoter segment for defining the minimal promoterand the crucial elements within; and 3, the electrophoresis mobility shift assay with specific antibodies forreconfirming the nature of the transcription factors and their cognate cis-elements. We have shown that theinteraction of an ATF/CREB element (-38 to -31) and its cognate transcription factors play a predominantrole in the promoter activity of the RNMTL1 gene. The secondary DNA structures of the ATF/CREBelement play a more vital role in the protein-DNA interaction. Finally, we reported a novel mechanismunderlying the YY1 mediated transcription repression, namely, the ATF/CREB dependent transcription-repression by YY1 is executed in absence of its own sequence-specific binding. | JIANXU JINGDEZHU 等 | 2002 | Cell Research2002，12，3： | 2 |
| 6 | Comparing the frequencies of restriction fragment length polymorphisms for dystrophin gene in Chinese with those from Japanese and Caucasian populations^1显示文摘The restriction fragment length polymorphisms distribution and frequency of dystrophin gene in Chinese were studied by using 14 subeiones of the entire 14kb eDNA for the dystrophin as hybridization probes. Allelie fragments were detected in hybridization patterns of PvuⅡ/la. TaqⅠ/2b-3, Taq Ⅰ/5b-7. and Xba Ⅰ/10. Among them. the allelic fragments (26kb and 3.8kb) in PvuⅡ/2b-3 pattern and the allelic fragments (10.0kb and 8.4kb) in Taq Ⅰ/5b-7 patterns had never been reported previously. Compared with the data from Caucasians and Japanese. it indicated that here was a significant difference (P <0.01) of the allelic fragment frequency in Taq Ⅰ/2b-3 and Xba Ⅰ/10 patterns between Chinese and Caucasians. The frequencies of allelic fragments A2 (5.6kb) in Taq Ⅰ/8 and A2 (10.7kb) in EcoR V/9 were high in Caucasians, yet had not been detected in Chinese, the differences were also highly significant. But in Chinese and Caucasians. the BIB2 allelic frequencies in Taq Ⅰ/5b-7 are the same. As to the frequency of the allelic fragments A1A2 and B1B2 in Pvu Ⅱ/1a. there was no significant difference between Chinese and Japenese. | YULong MINQINWANG QUNBINWANG WEIYIWANG YUMEIYANG JINGDEZHU SHOUYUANZHAO | 1993 | Cell Research1993，3，1： | 0 |
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