How Can the European Federation for Colposcopy Promote High Quality Colposcopy Throughout Europe?

Since its inception in 1998, the European Federation for Colposcopy (EFC) now comprises 26 member societies. Its principle aim is to promote high quality colposcopy throughout Europe with special emphasis on training, education and treatment. This review summarises EFC’s activities and achievements to date

Table_2_Identification of the Germline Mutation Profile in Esophageal Squamous Cell Carcinoma by Whole Exome Sequencing.XLS

Background: Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis and occurs with high frequency in China. The germline mutation profile in ESCC remains unclear, and therefore, the discovery of oncogenic alterations in ESCC is urgently needed. This study investigates the germline mutation profile and reveals associations among genotype-environment interactions in ESCC.Methods: Whole exome sequencing and follow-up analysis were performed in 77 matched tumor-normal ESCC specimens to examine the germline profiles. Additionally, associations among genotype-environment interactions were investigated.Results: We identified 84 pathogenic/likely pathogenic mutations and 51 rare variants of uncertain significance (VUS). Twenty VUS with InterVar evidence of a score of moderate pathogenicity (PM) 2/PM2+ supporting pathogenicity (PP) 1 were found to have pathogenic significance. CYP21A2 was the most frequently mutated gene, and the p.Gln319* variant was identified in 6.5% (5/77) of patients. The TP53 p.V197E mutation, located within the DNA binding domain, was found in 1.3% (1/77) of patients. In total, the 11.7% (9/77) of individuals with homologous recombination (HR) VUS were more likely to have well-differentiated tumors than those without (P = 0.003). The degree of lymph node metastasis was correlated with homologous recombination deficiency (HRD) and VUS group (P Conclusions: Our study identified the germline mutation profiles in ESCC, providing novel insights into the molecular pathogenesis of this disease. Our results may also serve as a useful resource for the exploration of the underlying mechanism of ESCC and may provide information for the prevention, diagnosis and risk management of ESCC.</p

Table_1_Identification of the Germline Mutation Profile in Esophageal Squamous Cell Carcinoma by Whole Exome Sequencing.XLSX

Background: Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis and occurs with high frequency in China. The germline mutation profile in ESCC remains unclear, and therefore, the discovery of oncogenic alterations in ESCC is urgently needed. This study investigates the germline mutation profile and reveals associations among genotype-environment interactions in ESCC.Methods: Whole exome sequencing and follow-up analysis were performed in 77 matched tumor-normal ESCC specimens to examine the germline profiles. Additionally, associations among genotype-environment interactions were investigated.Results: We identified 84 pathogenic/likely pathogenic mutations and 51 rare variants of uncertain significance (VUS). Twenty VUS with InterVar evidence of a score of moderate pathogenicity (PM) 2/PM2+ supporting pathogenicity (PP) 1 were found to have pathogenic significance. CYP21A2 was the most frequently mutated gene, and the p.Gln319* variant was identified in 6.5% (5/77) of patients. The TP53 p.V197E mutation, located within the DNA binding domain, was found in 1.3% (1/77) of patients. In total, the 11.7% (9/77) of individuals with homologous recombination (HR) VUS were more likely to have well-differentiated tumors than those without (P = 0.003). The degree of lymph node metastasis was correlated with homologous recombination deficiency (HRD) and VUS group (P Conclusions: Our study identified the germline mutation profiles in ESCC, providing novel insights into the molecular pathogenesis of this disease. Our results may also serve as a useful resource for the exploration of the underlying mechanism of ESCC and may provide information for the prevention, diagnosis and risk management of ESCC.</p

Data_Sheet_1_Identification of the Germline Mutation Profile in Esophageal Squamous Cell Carcinoma by Whole Exome Sequencing.docx

Background: Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis and occurs with high frequency in China. The germline mutation profile in ESCC remains unclear, and therefore, the discovery of oncogenic alterations in ESCC is urgently needed. This study investigates the germline mutation profile and reveals associations among genotype-environment interactions in ESCC.Methods: Whole exome sequencing and follow-up analysis were performed in 77 matched tumor-normal ESCC specimens to examine the germline profiles. Additionally, associations among genotype-environment interactions were investigated.Results: We identified 84 pathogenic/likely pathogenic mutations and 51 rare variants of uncertain significance (VUS). Twenty VUS with InterVar evidence of a score of moderate pathogenicity (PM) 2/PM2+ supporting pathogenicity (PP) 1 were found to have pathogenic significance. CYP21A2 was the most frequently mutated gene, and the p.Gln319* variant was identified in 6.5% (5/77) of patients. The TP53 p.V197E mutation, located within the DNA binding domain, was found in 1.3% (1/77) of patients. In total, the 11.7% (9/77) of individuals with homologous recombination (HR) VUS were more likely to have well-differentiated tumors than those without (P = 0.003). The degree of lymph node metastasis was correlated with homologous recombination deficiency (HRD) and VUS group (P Conclusions: Our study identified the germline mutation profiles in ESCC, providing novel insights into the molecular pathogenesis of this disease. Our results may also serve as a useful resource for the exploration of the underlying mechanism of ESCC and may provide information for the prevention, diagnosis and risk management of ESCC.</p

Promoter aberrant methylation status of <i>ADRA1A</i> is associated with hepatocellular carcinoma

The aim of our study was to explore the relationship between the methylation status of the alpha-1A adrenergic receptor (ADRA1A) gene and hepatocellular carcinoma (HCC). We combined our in-house data-set with the Cancer Genome Atlas (TCGA) data-set to screen and identify the methylation status and expression of adrenergic receptor (AR) genes in HCC. Immunohistochemistry and western blot were performed to assess the expression of ADRA1A in HCC cell lines and tissues. We further evaluated the methylation levels of the ADRA1A promoter region in 160 HCC patients using the Sequenom MassARRAY® platform and investigated the association between methylation of ADRA1A and clinical characteristics. The expression levels of ADRA1A mRNA and protein were significantly decreased in HCC tissues. Compared with that in paired normal tissues, the mean methylation level of the ADRA1A promoter region was significantly increased in tumour tissues from 160 HCC patients (25.2% vs. 17.0%, P ADRA1A mRNA in HCC cell lines. Moreover, hypermethylation of the ADRA1A gene in HCC samples was associated with clinical characteristics, including alcohol intake (P = 0.0097) and alpha-fetoprotein (P = 0.0411). Receiver operator characteristic (ROC) curve analysis demonstrated that the mean methylation levels of ADRA1A could discriminate between HCC tissues and adjacent non-cancerous tissues (AUC = 0.700, P ADRA1A gene hypermethylation might contribute to HCC initiation and is a promising biomarker for the diagnosis of HCC.</p

Association study of CACNA1C polymorphisms with large artery atherosclerotic stroke in Chinese Han population

<p><b>Aims</b> Ischemic stroke (IS) is one of the most common diseases of neurology and the main cause of death and disability in Chinese population. CACNA1C was considered to be involved in the process of atherosclerosis, but there was little information about the association between genotypic polymorphisms of CACNA1C and ischemic stroke. Our study was designed to elucidate the relationship between four single-nucleotide polymorphisms (SNPs) variants in CACNA1C gene and the risk of large-artery atherosclerotic (LAA) stroke patients.</p> <p><b>Methods</b> A total of 384 subjects were enrolled in this study, including 192 LAA stroke cases and 192 healthy controls. And four SNPs variants in CNCNA1C gene were genotyped using in-house developed multiplex tagged-amplicon deep sequencing (TAm-Seq). Statistical analysis were conducted using <i>χ</i>2 test and binary logistic regression analysis.</p> <p><b>Results</b> We found one variant was significantly associated with LAA stroke in the allele models (rs10848683, <i>p</i> = 0.036, OR = 1.371, 95%CI: 1.021–1.841). And rs10848683 was also found to associate with LAA stroke under recessive model (<i>p</i> = 0.027, OR = 0.618, 95% CI: 0.403–0.947) after adjustment for gender and age. We also found that significant difference existed between haplotypes (rs229961-rs215976-rs216008-rs10848683) and LAA stroke (C-T-C-C, <i>p</i> = 0.017, OR = 2.265, 95%CI: 1.136–4.518; G-C-C-C, <i>p</i> = 0.046, OR = 1.891, 95% CI: 1.003–3.565; C-T-C-T, <i>p</i> = 0.001, OR = 0.256, 95%CI: 0.101–0.645).</p> <p><b>Conclusion</b> The results suggested that there was a potential association between CNCNA1C gene and the risk factor of LAA stroke in Chinese Han population.</p

Supplementary File from Genome-wide DNA Methylation Analysis Reveals <i>GABBR2</i> as a Novel Epigenetic Target for <i>EGFR</i> 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment

Supplementary Methods and Figure legend of Supplementary Figure S1.</p

Table S3 from Genome-wide DNA Methylation Analysis Reveals <i>GABBR2</i> as a Novel Epigenetic Target for <i>EGFR</i> 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment

DNA methylation results of GABAA receptor families was relatively conservative before and after erlotinib treatment in both patients using methyl-sensitive cut counting sequencing (MSCC) screening method.</p

Figure S1 from Genome-wide DNA Methylation Analysis Reveals <i>GABBR2</i> as a Novel Epigenetic Target for <i>EGFR</i> 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment

The results proved that the whole-genome DNA methylation sequencing results were accurate and reliable from different aspects.</p

Table S1 from Genome-wide DNA Methylation Analysis Reveals <i>GABBR2</i> as a Novel Epigenetic Target for <i>EGFR</i> 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment

Data summary of methyl-sensitive cut counting sequencing (MSCC) sequencing of the 4 samples (8 libraries).</p