Search results for " Heterozygosity"
showing 10 items of 141 documents
A bi-allelic loss-of-function SARS1 variant in children with neurodevelopmental delay, deafness, cardiomyopathy, and decompensation during fever
2021
Aminoacyl-tRNA synthetases (aaRS) are ubiquitously expressed enzymes responsible for ligating amino acids to their cognate tRNA molecules through an aminoacylation reaction. The resulting aminoacyl-tRNA is delivered to ribosome elongation factors to participate in protein synthesis. Seryl-tRNA synthetase (SARS1) is one of the cytosolic aaRSs and catalyzes serine attachment to tRNASer . SARS1 deficiency has already been associated with moderate intellectual disability, ataxia, muscle weakness, and seizure in one family. We describe here a new clinical presentation including developmental delay, central deafness, cardiomyopathy, and metabolic decompensation during fever leading to death, in a…
Detection of the DCC gene product in normal and malignant colorectal tissues and its relation to a codon 201 mutation.
1998
Protein expression of the putative tumour-suppressor gene DCC on chromosome 18q was evaluated in a panel of 16 matched colorectal cancer and normal colonic tissue samples together with DCC mRNA expression and allelic deletions (loss of heterozygosity, LOH). Determined by a polymerase chain reaction (PCR)-LOH assay, 12 of the 16 (75%) cases were informative with LOH occurring in 2 of the 12 cases. For DCC mRNA, transcripts could be detected in all analysed normal tissues (eight out of eight) by RT-PCR, whereas 6 of the 15 tumours were negative. DCC protein expression, investigated by immunohistochemistry using the monoclonal antibody 15041 A directed against the intracellular domain, was hom…
Allelic loss but absence of mutations in the polyspecific transporter geneBWR1Aon 11p15.5 in hepatoblastoma
2004
Chromosomal region 11p15.5 shows frequent maternal allelic loss in embryonal tumors, including rhabdomyosarcoma (RMS), Wilms' tumor (WT) and hepatoblastoma (HB), consistent with the presence of at least one tumor suppressor gene in this region, which should be paternally imprinted, i.e., expressed from the maternal allele only. The BWR1A gene encodes a polyspecific transmembrane transporter and is located on 11p15.5. It is highly expressed in liver, paternally imprinted and was found to be mutated in an RMS cell line, making it a plausible tumor suppressor gene for HB. We therefore screened 62 HBs, 3 HB cell lines and 1 pediatric hepatocellular carcinoma for BWR1A mutations using single-str…
Pattern of secondary genomic changes in pancreatic tumors ofTgfα/Trp53+/−transgenic mice
2003
Trp53+/− mice overexpressing Tgfα in a pancreas-specific manner represent a well-established animal model for pancreatic cancer. In this study we analyzed 38 pancreatic adenocarcinomas of these mice for secondary genomic changes by comparative genomic hybridization (CGH), loss of heterozygosity (LOH) analysis, real-time PCR, and methylation-specific analysis. CGH screening of the tumors revealed a recurrent pattern of genomic changes. In more than 50% of the tumors, chromosome 11 was affected. The gain of the proximal part spans about 16 cM, including the genes for Egfr, Rel, and Stk10. The distal part of chromosome 11, which contains the Trp53 locus, was deleted. LOH analysis proved that a…
Low frequency of HLA haplotype loss associated with loss of heterozygocity in chromosome region 6p21 in clear renal cell carcinomas.
2004
HLA class I loss or downregulation is a widespread mechanism used by tumor cells to avoid tumor recognition by cytotoxic T lymphocytes favoring tumor immune escape. Multiple molecular mechanisms are responsible for these altered HLA class I tumor phenotypes. It has been described in different epithelial tumors that loss of heterozygosity (LOH) at chromosome region 6p21.3 is a frequent mechanism that leads to HLA haplotype loss, ranging between 40 and 50%, depending on the tumor entity analyzed. Here we have tested the frequency of LOH at 6p21 chromosome region in Renal Cell Carcinomas (RCC) of the clear cell and chromophobe subtype. A low frequency of HLA haplotype loss (6.6%) was found in …
Cytogenetic analysis of epithelial renal-cell tumors: Relationship with a new histopathological classification
1993
Renal-cell carcinomas (RCC) are clinically, histologically and cytogenetically very heterogeneous. The present histological WHO classification shows no clear correlation between histologic subtypes and specific chromosomal abnormalities. In 1986, a new classification was proposed by Thoenes and Storkel based on the cell type from which the tumor arises. They distinguish S cell types: clear-cell, chromophilic, chromophobic, ductus Bellini and oncocytic. Results of 105 primary tumors show that, in this new classification, there is a correlation between different subtypes of renal-cell tumor and specific chromosomal abnormalities at a microscopic and/or molecular level. The clear-cell compact …
Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection
2021
Background: Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis. Methods: 124 HCC patients, who underwent a primary hepatic …
Insights into Genetic Diversity, Runs of Homozygosity and Heterozygosity-Rich Regions in Maremmana Semi-Feral Cattle Using Pedigree and Genomic Data
2020
Semi-feral local livestock populations, like Maremmana cattle, are the object of renewed interest for the conservation of biological diversity and the preservation and exploitation of unique and potentially relevant genetic material. The aim of this study was to estimate genetic diversity parameters in semi-feral Maremmana cattle using both pedigree- and genomic-based approaches (FIS and FROH), and to detect regions of homozygosity (ROH) and heterozygosity (ROHet) in the genome. The average heterozygosity estimates were in the range reported for other cattle breeds (HE=0.261, HO=0.274). Pedigree-based average inbreeding (F) was estimated at 4.9%. The correlation was low between F and genomi…
GIST: Particular aspects related to cell cultures, xenografts, and cytogenetics
2006
In less than half a decade, gastrointestinal stromal tumors (GIST) have emerged from historical anonymity to become a model of kinase-targeted therapies. Approximately 80% to 85% of GISTs harbor activating mutations of the KIT or PDGFRA tyrosine kinase genes, and such mutations have predictive and prognostic value. In this regard, the in vitro and in vivo models have provided valuable tools for understanding the molecular pathology of this interesting neoplasm. This review charts particular aspects in the field of cell cultures and tumor xenografts in nude mice in GIST and their implication in the establishment of appropriate models for discovering and testing therapy. The cytogenetic featu…
Eight million years of maintained heterozygosity in chromosome homologs of cercopithecine monkeys
2020
In the Cercopithecini ancestor two chromosomes, homologous to human chromosomes 20 and 21, fused to form the Cercopithecini specific 20/21 association. In some individuals from the genus Cercopithecus, this association was shown to be polymorphic for the position of the centromere, suggesting centromere repositioning events. We set out to test this hypothesis by defining the evolutionary history of the 20/21 association in four Cercopithecini species from three different genera. The marker order of the various 20/21 associations was established using molecular cytogenetic techniques, including an array of more than 100 BACs. We discovered that five different forms of the 20/21 association w…