Search results for "MUTATION"
showing 10 items of 2830 documents
The Clinical Significance of Unknown Sequence Variants in BRCA Genes.
2010
Abstract: Germline mutations in BRCA1/2 genes are responsible for a large proportion of hereditary breast and/or ovarian cancers. Many highly penetrant predisposition alleles have been identified and include frameshift or nonsense mutations that lead to the translation of a truncated protein. Other alleles contain missense mutations, which result in amino acid substitution and intronic variants with splicing effect. The discovery of variants of uncertain/unclassified significance (VUS) is a result that can complicate rather than improve the risk assessment process. VUSs are mainly missense mutations, but also include a number of intronic variants and in-frame deletions and insertions. Over …
Genetic and epigenetic alterations as hallmarks of the intricate road to cancer.
2003
Despite the clonal origin of most tumors, their tremendous heterogeneity suggests that cancer progression springs from the combined forces of both genetic and epigenetic events, which produce variant clonal populations, together with the selective pressures of the microenvironment, which promote growth and, perhaps, dissemination of variants with a specific set of characteristics. Although the importance of genetic mutations in cancer has long been recognized, the role of epigenetic events has been suggested more recently. This review focuses on the genetic and epigenetic molecular mechanisms involved in cancer onset and progression, and discusses the possibility of new strategies in the de…
In the literature: October 2016
2016
A consortium on clinical and molecular stratification on oesophageal adenocarcinoma established in Britain has recently published in Nature Genetics , a whole-genomic sequencing analysis of more than 100 samples.1 Interestingly, they describe three distinct molecular subtypes with potential treatment relevance. This observation has also been verified in an independent validation cohort. Those three types are: (1) the ones showing homologous recombination and chromosome segregation pathways defects with enrichment of a BRCA signature. These tumours would be sensitive to DNA damaging agents, including neutron and photon irradiation with the addition of PARP inhibitors, (2) a group with high m…
The von Hippel-Lindau tumor suppressor gene
1997
Abstract The von Hippel-Lindau (VHL) disease is an inherited tumor susceptibility syndrome featuring a high variety of benign and malignant tumors. The gene has been localized and cloned at 3p25-26. Recent functional analysis defined the VHL gene product as an inhibitor of the transcription elongation process. Its possible involvement in the vascularization process may explain the histologic features of VHL tumors providing insight into basic mechanism of tumorigenesis. Direct genetic testing is available for patients affected with VHL. Seventy to eighty percent of the germline mutations expected could be detected. As first geno/phenotype correlations have been established, we are now begin…
Putative Breast Cancer Driver Mutations in TBX3 Cause Impaired Transcriptional Repression
2015
The closely related T-box transcription factors TBX2 and TBX3 are frequently overexpressed in melanoma and various types of human cancers, in particular, breast cancer. The overexpression of TBX2 and TBX3 can have several cellular effects, among them suppression of senescence, promotion of epithelial–mesenchymal transition, and invasive cell motility. In contrast, loss of function of TBX3 and most other human T-box genes causes developmental haploinsufficiency syndromes. Stephens and colleagues (1), by exome sequencing of breast tumor samples, identified five different mutations in TBX3, all affecting the DNA-binding T-domain. One in-frame deletion of a single amino acid, p.N212delN, was ob…
Analysis of extended genomic rearrangements in oncological research.
2007
Screening for genomic rearrangements is a fundamental task in the genetic diagnosis of many inherited disorders including cancer-predisposing syndromes. Several methods were developed for analysis of structural genomic abnormalities, some are targeted to the analysis of one or few specific loci, others are designed to scan the whole genome. Locus-specific methods are used when the candidate loci responsible for the specific pathological condition are known. Whole-genome methods are used to discover loci bearing structural abnormalities when the disease-associated locus is unknown. Three main approaches have been employed for the analysis of locus-specific structural changes. The first two a…
Delineating a new critical region for juvenile myoclonic epilepsy at the 22q11.2 chromosome.
2013
No abstract available
Mutations Involving the Transcription Factor CBFA1 Cause Cleidocranial Dysplasia
1997
AbstractCleidocranial dysplasia (CCD) is an autosomal-dominant condition characterized by hypoplasia/aplasia of clavicles, patent fontanelles, supernumerary teeth, short stature, and other changes in skeletal patterning and growth. In some families, the phenotype segregates with deletions resulting in heterozygous loss of CBFA1, a member of the runt family of transcription factors. In other families, insertion, deletion, and missense mutations lead to translational stop codons in the DNA binding domain or in the C-terminal transactivating region. In-frame expansion of a polyalanine stretch segregates in an affected family with brachydactyly and minor clinical findings of CCD. We conclude th…
Copy Number Variation and Missense Mutations of the Agouti Signaling Protein (<i>ASIP)</i> Gene in Goat Breeds with Different Coat Colors
2009
In goats, classical genetic studies reported a large number of alleles at the <i>Agouti</i> locus with effects on coat color and pattern distribution. From these early studies, the dominant <i>A</i><sup>Wt</sup> (white/tan) allele was suggested to cause the white color of the Saanen breed. Here, we sequenced the coding region of the goat <i>ASIP</i> gene in 6 goat breeds (Girgentana, Maltese, Derivata di Siria, Murciano-Granadina, Camosciata delle Alpi, and Saanen), with different coat colors and patterns. Five single nucleotide polymorphisms (SNPs) were identified, 3 of which caused missense mutations in conserved positions of the cysteine-ri…
Analysis of the melanocortin receptor 1 (MC1R) gene in Sicilian goat breeds
2010
AbstractMammalian coat colour is mainly determined by the distribution of two different types of melanins: pheomelanin (red/yellow pigments) and eumelanin (black pigments). Their synthesis is regulated by the melanocortin 1 receptor (MC1R/Extension locus) that binds the α-melanocyte-stimulating hormone (α-MSH) and the agouti signalling protein (ASIP, coded by the Agouti locus). In mammals, several studies have reported that loss-of-function mutations in MC1R lead to red/yellow pigmentation, while gain-of-function mutations lead to black/dark colours. Mutations at the Agouti locus exert, in general, epistatic interactions on the Extension locus. In goats, classical genetic studies have indic…