Changes of the Hepatic Proteome in Hepatitis B-Infected Mouse Model at Early Stages of Fibrosis

Liver fibrosis (LF) is the accumulation of extracellular matrix (ECM) proteins due to chronic liver injury. We used two-dimensional differential in-gel electrophoresis (2D-DIGE) to perform a comparative analysis of cytosolic and nuclear protein patterns of nontransgenic (NTg) and HBV transgenic (Tg) mice livers at early stages of fibrosis. We identified several candidate proteins, involved in a variety of pathways, which could be used as putative biomarkers for LF early detection

Comparative Proteomic Expression Profile in All-<i>trans</i> Retinoic Acid Differentiated Neuroblastoma Cell Line

Neuroblastoma (NB) is an infant tumor which frequently differentiates into neurons. We used two-dimensional differential in-gel electrophoresis (2D-DIGE) to analyze the cytosolic and nuclear protein expression patterns of LAN-5 cells following neuronal differentiating agent all-trans-retinoic acid treatment. We identified several candidate proteins, from which Gβ2 and Prefoldin 3 may have a role on NB development. These results strength the use of proteomics to discover new putative protein targets in cancer. Keywords: neuroblastoma • all-trans-retinoic acid • 2D-DIGE • LAN-5 human neuroblastoma cell lin

Image_2_CoDysAn: A Telemedicine Tool to Improve Awareness and Diagnosis for Patients With Congenital Dyserythropoietic Anemia.JPEG

Congenital Dyserythropoietic Anemia (CDA) is a heterogeneous group of hematological disorders characterized by chronic hyporegenerative anemia and distinct morphological abnormalities of erythroid precursors in the bone marrow. In many cases, a final diagnosis is not achieved due to different levels of awareness for the diagnosis of CDAs and lack of use of advanced diagnostic procedures. Researchers have identified five major types of CDA: types I, II, III, IV, and X-linked dyserythropoietic anemia and thrombocytopenia (XLDAT). Proper management in CDA is still unsatisfactory, as the different subtypes of CDA have different genetic causes and different but overlapping patterns of signs and symptoms. For this reason, we developed a new telemedicine tool that will help doctors to achieve a faster diagnostic for this disease. Using open access code, we have created a responsive webpage named CoDysAn (Congenital Dyserythropoietic Anemia) that includes practical information for CDA awareness and a step-by-step diagnostic tool based on a CDA algorithm. The site is currently available in four languages (Catalan, Spanish, Italian, and English). This telemedicine webpage is available at http://www.codysan.eu.</p

Supplementary Data from Somatic Mutations Enriched in <i>Cis</i>-Regulatory Elements Affect Genes Involved in Embryonic Development and Immune System Response in Neuroblastoma

Supplementary Data from Somatic Mutations Enriched in Cis-Regulatory Elements Affect Genes Involved in Embryonic Development and Immune System Response in Neuroblastom

Table_1_CoDysAn: A Telemedicine Tool to Improve Awareness and Diagnosis for Patients With Congenital Dyserythropoietic Anemia.DOCX

Congenital Dyserythropoietic Anemia (CDA) is a heterogeneous group of hematological disorders characterized by chronic hyporegenerative anemia and distinct morphological abnormalities of erythroid precursors in the bone marrow. In many cases, a final diagnosis is not achieved due to different levels of awareness for the diagnosis of CDAs and lack of use of advanced diagnostic procedures. Researchers have identified five major types of CDA: types I, II, III, IV, and X-linked dyserythropoietic anemia and thrombocytopenia (XLDAT). Proper management in CDA is still unsatisfactory, as the different subtypes of CDA have different genetic causes and different but overlapping patterns of signs and symptoms. For this reason, we developed a new telemedicine tool that will help doctors to achieve a faster diagnostic for this disease. Using open access code, we have created a responsive webpage named CoDysAn (Congenital Dyserythropoietic Anemia) that includes practical information for CDA awareness and a step-by-step diagnostic tool based on a CDA algorithm. The site is currently available in four languages (Catalan, Spanish, Italian, and English). This telemedicine webpage is available at http://www.codysan.eu.</p

Case-Control study of <i>IL-6</i>–176 (G>C) SNP.

a<p>P-value and OR obtained by Armitage's trend test.</p

Impact of Interleukin-6 –174 G>C Gene Promoter Polymorphism on Neuroblastoma

<div><p>Background</p><p>Common variants in DNA may predispose to onset and progression of neuroblastoma (NB). The genotype GG of single nucleotide polymorphism (SNP) rs1800795 (−174 G>C) in interleukin (IL)-6 promoter has been associated with lower survival of high-risk NB.</p><p>Result</p><p>To evaluate the impact of <i>IL-6</i> SNP rs1800795 on disease risk and phenotype, we analyzed 326 Italian NB patients and 511 controls. Moreover, we performed <i>in silico</i> and quantitative Real Time (qRT)-PCR analyses to evaluate the influence of the SNP on gene expression in 198 lymphoblastoid cell lines (LCLs) and in 31 NB tumors, respectively. Kaplan-Meier analysis was used to verify the association between <i>IL-6</i> gene expression and patient survival. We found that <i>IL-6</i> SNP is not involved in susceptibility to NB development. However, our results show that a low frequency of genotype CC is significantly associated with a low overall survival, advanced stage, and high-risk phenotype. The <i>in silico</i> (<i>p</i> = 2.61×10⁻⁵) and qRT-PCR (<i>p</i> = 0.03) analyses showed similar trend indicating that the CC genotype is correlated with increased level of <i>IL-6</i> expression. In report gene assay, we showed that the −174 C variant had a significantly increased transcriptional activity compared with G allele (<i>p</i> = 0.0006). Moreover, Kaplan-Meier analysis demonstrated that high levels of <i>IL-6</i> are associated with poor outcome in children with NB in two independent gene expression array datasets.</p><p>Conclusions</p><p>The biological effect of SNP <i>IL-6</i>–174 G>C in relation to promotion of cancer progression is consistent with the observed decreased survival time. The present study suggests that SNP <i>IL-6</i>–174 G>C may be a useful marker for NB prognosis.</p></div

Supplementary Data from Somatic Mutations Enriched in <i>Cis</i>-Regulatory Elements Affect Genes Involved in Embryonic Development and Immune System Response in Neuroblastoma

Supplementary Data from Somatic Mutations Enriched in Cis-Regulatory Elements Affect Genes Involved in Embryonic Development and Immune System Response in Neuroblastom

Characteristics of NB patients stratified per <i>IL-6</i> -176 (G>C) SNP genotype.

<p>N.A.  =  not available.</p>a<p>p-values and ORs from comparison of allelic frequencies.</p>b<p>p-values and ORs from comparison of genotype frequencies (GG/GC vs CC).</p>c<p>p-values and ORs from comparison of stage 1+2 patients vs stage 3+4 patients.</p

Table3_Clinical exome-based panel testing for medically actionable secondary findings in a cohort of 383 Italian participants.xlsx

Background: Next-generation sequencing-based genetic testing represents a great opportunity to identify hereditary predispositions to specific pathological conditions and to promptly implement health surveillance or therapeutic protocols in case of disease. The term secondary finding refers to the active search for causative variants in genes associated with medically actionable conditions.Methods: We evaluated 59 medically actionable ACMG genes using a targeted in silico analysis of clinical exome sequencing performed in 383 consecutive individuals referred to our Medical Genetics Unit. A three-tier classification system of SFs for assessing their clinical impact and supporting a decision-making process for reporting was established.Results: We identified SFs with high/moderate evidence of pathogenicity in 7.0% (27/383) of analyzed subjects. Among these, 12/27 (44.4%) were carriers of a high-risk recessive disease allele. The most represented disease domains were cancer predisposition (33.3%), cardiac disorders (16.7%), and familial hypercholesterolemia (12.5%).Conclusion: Although still debated, ensuring during NGS-based genetic testing an opportunistic screening might be valuable for personal and familial early management and surveillance of medically actionable disorders, the individual’s reproductive choices, and the prevalence assessment of underestimated hereditary genetic diseases.</p