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Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes ( SFRP2 , SFRP4 , SFRP5 , DKK1 , DKK2 , and APC ) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2 , SFRP4 , DKK1 , and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of β-catenin, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

Purpose: The aim of this study was to investigate polymorphisms in DNA repair genes as potential predictive factors among Chinese cervical cancer patients., Methods: A total of 72 patients with cervical carcinoma, who received cisplatin-based chemoradiotherapy and whose responses were evaluated by Response Evaluation Criteria in Solid Tumors, were included. The association between response to chemoradiotherapy and the genotypes for 29 single-nucleotide polymorphisms (SNPs) in 25 DNA repair genes were analyzed., Results: A minor allele of SNP rs9350 in the exonuclease 1 gene was associated with a better response rate, regardless of age and tumor stage (odds ratio, 8.316; p=0.002)., Conclusion: SNP rs9350 in the exonuclease 1 gene is involved in inter-individual differences in the response to cisplatin-based chemoradiotherapy, in patients with cervical carcinoma., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The CYP2A6*4 allele, characterized as the whole deletion of this gene, is closely associated with nicotine dependence, cancer susceptibility, and drug responsiveness. The frequency of this molecular variant differs across populations. Although genetic polymorphisms of CYP2A6*4 and its functional results have been reported in Chinese Han population, the allele frequency of CYP2A6*4 was largely unknown in other Chinese ethnic population. In this study, we investigated the allele frequency of CYP2A6*4 in four main ethnic groups of China based on our newly developed quantitative real-time PCR assay. The frequencies of the CYP2A6*4 allele were 7.9%, 15%, 0% and 2% in Han (N=120), Uighur (N=100), Bouyei (N=100) and Tibetan (N=100) (P<0.0001), respectively. This work greatly expanded our understanding of the distribution of CYP2A6*4 in Chinese population and provided more information of different ethnic population's smoking behavior and also in disease susceptibility and drug response., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to investigate the predictive value of common genetic alterations of PI3K/AKT/mTOR and Ras/Raf/MAPK pathways in patients with locally advanced cervical squamous cell carcinoma (LACSCC) treated with cisplatin-based concurrent chemoradiotherapy (CCRT)., Methods: Patients with LACSCC, treated at a single institution with CCRT were eligible for this retrospective study. A total of sixty pre-treatment tumor biopsies were retrieved. Somatic mutations were detected by pyrosequencing and CNV was determined by quantitative realtime PCR. The association of genetic alterations with clinicopathological characteristics and treatment response were analyzed., Results: Patients without genetic alterations (mutations or amplification) of PIK3CA had a significantly higher response rate than patients with these alterations (p=0.006). In the logistic regression analysis, PIK3CA genetic alterations retained an independent factor in predicting response to CCRT., Conclusions: Somatic mutations and copy number amplification of PIK3CA were associated with response to CCRT in patients with cervical squamous cell carcinoma., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Acquired resistance to endocrine-based therapies occurs in virtually all estrogen receptor-α (ERα, encoded by ESR1) positive breast cancer patients. The underlying molecular mechanism is attributed to the activating mutations in ESR1. These mutations provide an exciting opportunity for the development of new antagonists that specifically inhibit the mutant proteins. Therefore, accurate detection of ESR1 mutations is of critical importance in clinical practice., Materials and Methods: We carried out a single tube, multiplex allele-specific real-time PCR assay for the detection of four ESR1 mutations (Y537S, Y537C, Y537N, and D538G)., Results: The assay was found to be highly specific and sensitive. With this assay, as low as 1% mutant DNA template in wild type DNA could be detected. Fifteen DNA samples were prepared from archived formalin-fixed paraffin-embedded metastatic breast cancer biopsies. They were further screened with this assay, and three samples were identified as ESR1 mutant. The results were validated with pyrosequencing and complete concordance was observed between the two assays., Conclusion: The multiplex allele-specific real-time PCR assay provides a rapid and reliable diagnostic tool for accurate detection of ESR1 mutations. This procedure may be used in the clinical treatment of breast cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The CYP2A6*4 allele, characterized as the whole deletion of this gene, is closely associated with nicotine dependence, cancer susceptibility, and drug responsiveness. It has long been a significant challenge for pharmacogenetics scientists to develop a reliable method to detect this molecular variant due to its high homology with its homologous genes CYP2A6 and CYP2A3 in the clinical setting. Here, we introduce a quantitative real-time PCR assay that specifically amplifies CYP2A6 by designing a specific set of primers and the probe, which effectively prevent the amplification of the CYP2A7 and CYP2A13 alleles. CYP2A6 gene copy numbers were normalized to albumin (ALB) which was co-amplified simultaneously in a single-tube duplex reaction and at a setting as the internal reference gene. The established assay was validated with a selection of previously genotyped DNA samples, which harbored none, one or two CYP2A6 gene copies. The results were in complete concordance with previously published data and no overlap between the three groups was observed. Further analysis of a cohort of 120 samples revealed high specificity and sensitivity of this assay as demonstrated by the agreement of determined gene copy numbers in all of the cases. In conclusion, this novel assay allows reliable and sensitive detection of the CYP2A6 gene deletion, which will be useful for pharmacogenetics studies and routine clinical settings., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The development of pharmacogenomics has created an urgent need for robust molecular characterization. And it has become a challenge to develop suitable detecting methods for routine clinical use., Aim: The aim of the current study is to develop a simple and reliable TYMS 1494del6 polymorphism genotyping assay by duplex scorpion primers in the Chinese Han population., Method: We evaluated the performance of the duplex scorpion primer assay in the genotyping of TYMS 1494del6 polymorphism and screened 54 DNA samples of the Chinese Han population. The results were further validated by pyrosequencing., Results: The duplex scorpion primer assay showed high specificity and accuracy for genotyping TYMS 1494del6 polymorphism. Complete concordance was observed between the duplex scorpion primer assay and pyrosequencing. The frequency of the TYMS +6 bp allele was 34% and the -6 bp allele was 66% in 54 Chinese Han population DNA samples., Conclusion: The duplex scorpion primer assay provides a rapid, reliable and high-throughput method to genotype TYMS 1494del6 polymorphism in the Chinese Han population., (Copyright © 2014 Elsevier Inc. All rights reserved.)