Search results for "25"
showing 10 items of 3263 documents
The copy number variant involving part of the α7 nicotinic receptor gene contains a polymorphic inversion.
2008
The alpha7 nicotinic acetylcholine receptor gene (CHRNA7) is located at 15q13-q14 in a region that is strongly linked to the P50 sensory gating deficit, an endophenotype of schizophrenia and bipolar disorder. Part of the gene is a copy number variant, due to a duplication of exons 5-10 and 3' sequence in CHRFAM7A, which is present in many but not all humans. Maps of this region show that the two genes are in opposite orientation in the individual mainly represented in the public access human DNA sequence database (Build 36), suggesting that an inversion had occurred since the duplication. We have used fluorescent in situ hybridization to investigate this putative inversion. Analysis of inte…
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 …
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…
Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype
2007
Abstract Background Genetic instability is a hallmark of tumours and preneoplastic lesions. The predominant form of genome instability in human cancer is chromosome instability (CIN). CIN is characterized by chromosomal aberrations, gains or losses of whole chromosomes (aneuploidy), and it is often associated with centrosome amplification. Centrosomes control cell division by forming a bipolar mitotic spindle and play an essential role in the maintenance of chromosomal stability. However, whether centrosome amplification could directly cause aneuploidy is not fully established. Also, alterations in genes required for mitotic progression could be involved in CIN. A major candidate is represe…
CENPA overexpression promotes genome instability in pRb-depleted human cells
2009
Abstract Background Aneuploidy is a hallmark of most human cancers that arises as a consequence of chromosomal instability and it is frequently associated with centrosome amplification. Functional inactivation of the Retinoblastoma protein (pRb) has been indicated as a cause promoting chromosomal instability as well centrosome amplification. However, the underlying molecular mechanism still remains to be clarified. Results Here we show that pRb depletion both in wild type and p53 knockout HCT116 cells was associated with the presence of multipolar spindles, anaphase bridges, lagging chromosomes and micronuclei harbouring whole chromosomes. In addition aneuploidy caused by pRb acute loss was…
TCR Clonality and Genomic Instability Signatures as Prognostic Biomarkers in High Grade Serous Ovarian Cancer.
2021
Simple Summary High-grade serous ovarian carcinoma (HGSC) could be analyzed with a molecular stratification defined by different genomic instability signatures associated with specific mutational process and prognostic biomarkers. Immune infiltrate is known to be a robust biomarker in HGSC. We aimed to investigate immune parameters according to genomic instability signatures. We observed that homologous recombination deficiency positive, copy cumber variant signature 7 and TCR (T cells receptor) clonality are good prognostic biomarkers in HGSC. Combining TCR clonality and genomic instability signature or T cell infiltration improved the prognostic value compared to each variable taken alone…
Bypass of cell cycle arrest induced by transient DNMT1 post-transcriptional silencing triggers aneuploidy in human cells
2012
Abstract Background Aneuploidy has been acknowledged as a major source of genomic instability in cancer, and it is often considered the result of chromosome segregation errors including those caused by defects in genes controlling the mitotic spindle assembly, centrosome duplication and cell-cycle checkpoints. Aneuploidy and chromosomal instability has been also correlated with epigenetic alteration, however the molecular basis of this correlation is poorly understood. Results To address the functional connection existing between epigenetic changes and aneuploidy, we used RNA-interference to silence the DNMT1 gene, encoding for a highly conserved member of the DNA methyl-transferases. DNMT1…
Network for blood pressure research in children and adolescents (COST Action CA 19115)
2021
High blood pressure is a clearly established modifiable risk factor for cardiovascular and renal disease. Although most of its adverse effects develop in adulthood, it has become clear that high BP is a lifelong problem that can manifest early in life. While few would dispute the importance of taking effective steps to identify and manage this condition in middle-aged and elderly individuals, relatively little attention has been paid to the problem of high BP in children and adolescents.Therefore, the development of actions focused on early childhood, childhood and adolescence and the investigation of the underlying causes of this epidemic are of utmost importance. There is a pressing need …
Childhood Sports Participation Is Associated With Health-Related Quality of Life in Young Men: A Retrospective Cross-Sectional Study
2021
The aim of the study was to examine whether sports participation (SP), engagement in competitive sports (CS) and the type of sport undertaken at the age of 12 are associated with the physical and the mental components of health-related quality of life (HRQoL) in young adulthood. The data were collected using questionnaires prior to a compulsory military refresher training course in Finland. The sample consisted of 784 men (mean age 26 years). HRQoL was measured with RAND 36 and childhood sports participation with a series of questions. Data were analysed with logistic regression. Higher frequency of SP, participation in district level CS, performing team, endurance or extreme sports and pla…
The Latvian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).
2017
The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Latvian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their paren…