Number Of Specific Mutations Research Articles

HNRNPCL1, PRAMEF1, CFAP74, and DFFB: Common Potential Biomarkers for Sporadic and Suspected Lynch Syndrome Endometrial Cancer.

PurposeTo investigate the genes of patients with sporadic endometrial cancer (EC) and suspected Lynch syndrome (LS)-related EC in the Chinese population. Identification of meaningful mutation sites can provide theoretical basis for molecular targeted therapy, aiming to improve the prognosis of patients with EC.MethodsWe recruited 388 patients with EC for mismatch repair (MMR) immunohistochemistry and MLH1 methylation analysis. Based on the results, they were divided into four groups: MMR without deletion group (sporadic EC group 1); MLH1&PMS2 deletion and MLH1 methylation group (sporadic EC group 2); MSH2 and/or MSH6 deletion group (suspected LS group); and unclassified group (remainder cases). Patients from each group were randomly screened for whole-exome sequencing detection. Genome Analysis Toolkit, VarScant, MuTect, and CONTRA were used to detect the insertions/deletions, single nucleotide polymorphisms, and copy number variations. Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed with Database for Annotation, Visualization and Integrated Discovery. Protein–protein interaction analysis was accomplished through the STRING database.ResultsThe MMR immunohistochemistry results were positive (without MMR deletion) and negative in 299 patients and 89 patients, respectively. The 32, 10, 13, and 7 patients in the sporadic EC group 1, sporadic EC group 2, suspected LS group, and unclassified group were randomly selected for whole-exome sequencing, respectively. These three groups had a total of 86 common mutation sites, which were distributed on 26 genes. Among the top 30 common high-frequency mutation sites, 12, 5, 4, and 3 mutation sites were located on HNRNPCL1, PRAMEF1, HNRNPCL2, and CFAP74, respectively. Protein–protein interaction analysis showed that DFFB was associated with the most genes. There were some differences in the number of specific mutations in the families of different LS-related EC proband.ConclusionHNRNPCL1, PRAMEF1, CFAP74, and DFFB may be potential biomarkers for EC or LS-related EC.

Prediction of potential drivers connecting different dysfunctional levels in lung adenocarcinoma via a protein–protein interaction network

Lung cancer is a serious disease that threatens an affected individual's life. Its pathogenesis has not yet to be fully described, thereby impeding the development of effective treatments and preventive measures. “Cancer driver” theory considers that tumor initiation can be associated with a number of specific mutations in genes called cancer driver genes. Four omics levels, namely, (1) methylation, (2) microRNA, (3) mutation, and (4) mRNA levels, are utilized to cluster cancer driver genes. In this study, the known dysfunctional genes of these four levels were used to identify novel driver genes of lung adenocarcinoma, a subtype of lung cancer. These genes could contribute to the initiation and progression of lung adenocarcinoma in at least two levels. First, random walk with restart algorithm was performed on a protein–protein interaction (PPI) network constructed with PPI information in STRING by using known dysfunctional genes as seed nodes for each level, thereby yielding four groups of possible genes. Second, these genes were further evaluated in a test strategy to exclude false positives and select the most important ones. Finally, after conducting an intersection operation in any two groups of genes, we obtained several inferred driver genes that contributed to the initiation of lung adenocarcinoma in at least two omics levels. Several genes from these groups could be confirmed according to recently published studies. The inferred genes reported in this study were also different from those described in a previous study, suggesting that they can be used as essential supplementary data for investigations on the initiation of lung adenocarcinoma. This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang.

Determination of antigenic properties of vaccine derived poliovirus strains

In this study, the immunity level of the southern Greek population in the 1–10-year, 11–20-year, 21–30-year and 31–40-year age groups with regard to Sabin vaccine strains and a collection of 11 recombinant and three non-recombinant poliovirus vaccine strains was determined. The results showed the lowest neutralization titre in the 21–30-year-age group against poliovirus type 3. Moreover, the capsid coding region of OPV (oral poliovirus vaccine) derivatives was sequenced in order to identify mutations that might lead to antigenic changes. In Sabin-1 derivatives a tendency of accumulation of mutations was observed in or near antigenic sites while in Sabin-2 and Sabin-3 derivatives in sites known to be involved in restoring neurovirulence or eliminating their temperature-sensitive phenotype. It was concluded that the combination of mutations in the capsid coding region and not the number of specific mutations in antigenic sites determines the antigenic properties of OPV derivatives and their reactivity with human sera.

Different α1-Adrenergic Receptor Sequences Required for Activating Different Gα Subunits of Gq Class of G Proteins

In order to understand the specific interactions between receptors and guanine nucleotide-binding regulatory protein (G proteins), we attempted to delineate the alpha 1 B-adrenergic receptor sequences involved in activation of the alpha subunits of the Gq class of G proteins. A number of specific mutations were introduced into the third inner loop of the receptor, and the mutants were tested for their abilities to activate different G alpha subunits of the Gq class. Our results indicate that the receptor sequences required for activating G alpha q/11, G alpha 14, or G alpha 16 are different. The sequence extending from residues Lys240 to His252 is required for activation of G alpha q/11, but not for activation of G alpha 14 or G alpha 16. Two segments in the third loop of the receptor are required for activation of G alpha 14: one is located at the N terminus of the loop ending at residue Asn226, and the other is located at the C terminus of the loop starting from residue Ser278. The latter contains a BBXXB motif, which is apparently critical for G alpha 14 coupling, but not for G alpha 16 or G alpha q/11 coupling. Furthermore, the three amino acids stretch (Tyr217 to Val219) included in the N-terminal segment is not only required for G alpha 14 coupling, but also for G alpha q/11 coupling. It may be involved to some extent in G alpha 16 coupling as well.