Search results for "mutations"

Disparity between Inter-Patient Molecular Heterogeneity and Repertoires of Target Drugs Used for Different Types of Cancer in Clinical Oncology

2020

Inter-patient molecular heterogeneity is the major declared driver of an expanding variety of anticancer drugs and personalizing their prescriptions. Here, we compared interpatient molecular heterogeneities of tumors and repertoires of drugs or their molecular targets currently in use in clinical oncology. We estimated molecular heterogeneity using genomic (whole exome sequencing) and transcriptomic (RNA sequencing) data for 4890 tumors taken from The Cancer Genome Atlas database. For thirteen major cancer types, we compared heterogeneities at the levels of mutations and gene expression with the repertoires of targeted therapeutics and their molecular targets accepted by the current guideli…

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 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…

Coat colours in the Massese sheep breed are associated with mutations in the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes

2012

Massese is an Italian dairy sheep breed characterized by animals with black skin and horns and black or apparent grey hairs. Owing to the presence of these two coat colour types, this breed can be considered an interesting model to evaluate the effects of coat colour gene polymorphisms on this phenotypic trait. Two main loci have been already shown to affect coat colour in sheep: Agouti and Extension coding for the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes, respectively. The Agouti locus is affected by a large duplication including the ASIP gene that may determine the Agouti white and tan allele (A(Wt)). Other disrupting or partially inactivating mutations ha…

Rubinstein-Taybi syndrome in first cousins with different de novo mutations

2010

Gray code for permutations with a fixed number of cycles

2007

AbstractWe give the first Gray code for the set of n-length permutations with a given number of cycles. In this code, each permutation is transformed into its successor by a product with a cycle of length three, which is optimal. If we represent each permutation by its transposition array then the obtained list still remains a Gray code and this allows us to construct a constant amortized time (CAT) algorithm for generating these codes. Also, Gray code and generating algorithm for n-length permutations with fixed number of left-to-right minima are discussed.

A catalog of HLA type, HLA expression, and neo-epitope candidates in human cancer cell lines

2014

Cancer cell lines are a tremendous resource for cancer biology and therapy development. These multipurpose tools are commonly used to examine the genetic origin of cancers, to identify potential novel tumor targets, such as tumor antigens for vaccine devel-opment, and utilized to screen potential therapies in preclinical studies. Mutations, gene expression, and drug sensitivity have been determined for many cell lines using next-generation sequencing (NGS). However, the human leukocyte antigen (HLA) type and HLA expression of tumor cell lines, characterizations necessary for the development of cancer vaccines, have remained largely incomplete and, such information, when available, has been …

Association of Variants in the SPTLC1 Gene with Juvenile Amyotrophic Lateral Sclerosis

2021

Key Points Question What genetic variants are associated with juvenile amyotrophic lateral sclerosis (ALS)? Findings In this family-based genetic study, exome sequencing was performed in 3 patients diagnosed with juvenile ALS and failure to thrive; this identified de novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient). Variants in SPTLC1 are a known cause of hereditary sensory and autonomic neuropathy, type 1A, and these data extend the phenotype associated with this gene. Meaning De novo variants in the SPTLC1 gene are associated with juvenile ALS, a fatal neurological disorder.

Analysis of Ki-Ras mutations in stage I rectal carcinomas and respective regional lymph nodes.

2007

In this work we show that the percentage of Ki-RAS mutations in codons 12 and 13 in rectal cancer are sensibly lower than in colon cancer, providing further evidence that these two kinds of tumors should be considered two different entities. Moreover, we show that the detection in regional lymph nodes of the same mutation of primary tumor might represent an indicator of lymph nodes metastasis in rectal carcinoma not detected in routine histologic examination.

On modeling the immune competition with Darwinian dynamics

Mathematical and computational models are increasingly used in this century to help modeling of living systems. Mathematical modeling presents many methods for studying and analyzing the behavior of biological systems, in particular, cellular systems. As Bellomo (2008), Bellouquid and Delitala (2006), suggest " The modeling of living systems is not an easy task, it requests technically complex mathematical methods to deal with the inner complexity of biological systems which exhibit features and behaviors very different from those of inert matter". The mathematical approach used in this dissertation is based on the Kinetic Theory of Active Particles (KTAP), that has been specifically develo…