Search results for "Exons"
showing 10 items of 197 documents
Impact of BRAF and RAS mutations on first-line efficacy of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab: analysis of the FIRE-3 (AIO KRK-03…
2017
Abstract Background RAS and BRAF mutations have been identified as negative prognostic factors in metastatic colorectal cancer. Efficacy of 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) plus bevacizumab in patients with RAS-mutant tumours needs to be further evaluated. Whether to treat patients with BRAF-mutant tumours with either bevacizumab or anti-epidermal growth factor receptor (EGFR) antibodies remains unclear. Methods Patients treated within the FIRE-3 trial were retrospectively tested for BRAF and RAS mutations using formalin fixated paraffin embedded (FFPE) tumour material applying pyrosequencing for KRAS and NRAS exon 2, 3 and 4 mutations as far as for BRAF mutations. Survival …
Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing : results of the RING observational trial
2020
Plasma samples from 72 EGFR‐mutant advanced NSCLC patients, collected upon progression to first‐line TKI, were analyzed by seven methodologies (two NGS‐based methods, three high‐sensitivity PCR‐based platforms, and two FDA‐approved methods). Our study demonstrates a good to excellent agreement between methodologies and supports the use of liquid biopsies for therapy decision‐making.
Characterisation of CDKL5 Transcript Isoforms in Human and Mouse.
2016
Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brai…
Apert Syndrome With FGFR2 758 C > G Mutation: A Chinese Case Report
2018
Background: Apert syndrome is considered as one of the most common craniosynostosis syndromes with a prevalence of 1 in 65,000 individuals, and has a close relationship with point mutations in FGFR2 gene.Case report: Here, we described a Apert syndrome case, who was referred to genetic consultation in our hospital with the symptom of craniosynostosis and syndactyly of the hands and feet. Craniosynostosis, midfacial retrusion, steep wide forehead, larger head circumference, marked depression of the nasal bridge, short and wide nose and proptosis could be found obviously, apart from these, ears were mildly low compared with normal children and there was no cleft lip and palate. Mutation was i…
Genomic structure and functional characterization of the human ADAM10 promoter
2005
The ADAM10 gene encodes a membrane-bound disintegrin-metalloproteinase, which, after overexpression in an Alzheimer disease (AD) mouse model, prevents amyloid pathology and improves long-term potentiation and memory. Because enhancing ADAM10 expression appears to be a reasonable approach for treatment of AD, we functionally analyzed the ADAM10 gene. Both human and mouse ADAM10 genes comprise approximately 160 kbp, are composed of 16 exons, and are evolutionarily highly conserved within 500 bp upstream of either translation initiation site. By using luciferase reporter assays, we demonstrate that nucleotides -2179 to -1 upstream of the human ADAM10 translation initiation site represent a fun…
Genomic organization and promoter characterization of the gene encoding a putative endoplasmic reticulum chaperone, ERp29
2002
Abstract ERp29 is a soluble protein localized in the endoplasmic reticulum (ER) of eukaryotic cells, which is conserved in all mammalian species. The N-terminal domain of ERp29 displays sequence and structural similarity to the protein disulfide isomerase despite the lack of the characteristic double cysteine motif. Although the exact function of ERp29 is not yet known, it was hypothesized that it may facilitate folding and/or export of secretory proteins in/from the ER. ERp29 is induced by ER stress, i.e. accumulation of unfolded proteins in the ER. To gain an insight into the mechanisms regulating ERp29 expression we have cloned and characterized the rat ERp29 gene and studied in details …
Sequence of a sea urchin hsp70 gene and its 5' flanking region.
1990
We report the nucleotide sequence of a 4470-bp fragment derived from a sea urchin genomic clone containing part of a heat-shock protein 70 (Hsp70)-encoding gene. This fragment, named hsp70 gene II, contains 1271 bp of the flanking region and 3299 bp of structural gene sequence interrupted by five introns and encoding the N-terminal 371 amino acids (aa) of the protein. The 5' flanking region contains a putative TATA element, two CCAAT boxes, four heat-shock consensus sequence elements (hse) and one consensus sequence for binding of Sp1. Remarkable homologies were observed for deduced aa sequence and intron-exon organization between hsp70 gene II and rat hsc73 gene.
A computational method for studying the relation between alternative splicing and DNA methylation.
2015
Alternative splicing is an important mechanism in eukaryotes that expands the transcriptome and proteome significantly. It plays an important role in a number of biological processes. Understanding its regulation is hence an important challenge. Recently, increasing evidence has been collected that supports an involvement of intragenic DNA methylation in the regulation of alternative splicing. The exact mechanisms of regulation, however, are largely unknown, and speculated to be complex: different methylation profiles might exist, each of which could be associated with a different regulation mechanism. We present a computational technique that is able to determine such stable methylation pa…
Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC-PGL syndromes: a clinicopathological and m…
2014
ObjectiveAlthough the succinate dehydrogenase (SDH)-related tumor spectrum has been recently expanded, there are only rare reports of non-pheochromocytoma/paraganglioma tumors in SDHx-mutated patients. Therefore, questions still remain unresolved concerning the aforementioned tumors with regard to their pathogenesis, clinicopathological phenotype, and even causal relatedness to SDHx mutations. Absence of SDHB expression in tumors derived from tissues susceptible to SDH deficiency is not fully elucidated.Design and methodsThree unrelated SDHD patients, two with pituitary adenoma (PA) and one with papillary thyroid carcinoma (PTC), and three SDHB patients affected by renal cell carcinomas (RC…
Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS
2010
Summary Using exome sequencing, we identified a p.R191Q amino acid change in the valosin-containing protein ( VCP ) gene in an Italian family with autosomal dominantly inherited amyotrophic lateral sclerosis (ALS). Mutations in VCP have previously been identified in families with Inclusion Body Myopathy, Paget disease, and Frontotemporal Dementia (IBMPFD). Screening of VCP in a cohort of 210 familial ALS cases and 78 autopsy-proven ALS cases identified four additional mutations including a p.R155H mutation in a pathologically proven case of ALS. VCP protein is essential for maturation of ubiquitin-containing autophagosomes, and mutant VCP toxicity is partially mediated through its effect on…