Unique features of the transcriptional response to model aneuploidy in human cells

Episode von Medizin - Open Access LMU - Teil 22/22 von Ludwig-Maximilians-Universität München · 1. Januar 2014

Background: Aneuploidy, a karyotype deviating from multiples of a haploid chromosome set, affects the physiology of eukaryotes. In humans, aneuploidy is linked to pathological defects such as developmental abnormalities, mental retardation or cancer, but the underlying mechanisms remain elusive. There are many different types and origins of aneuploidy, but whether there is a uniform cellular response to aneuploidy in human cells has not been addressed so far. Results: Here we evaluate the transcription profiles of eleven trisomic and tetrasomic cell lines and two cell lines with complex aneuploid karyotypes. We identify a characteristic aneuploidy response pattern defined by upregulation of genes linked to endoplasmic reticulum, Golgi apparatus and lysosomes, and downregulation of DNA replication, transcription as well as ribosomes. Strikingly, complex aneuploidy elicits the same transcriptional changes as trisomy. To uncover the triggers of the response, we compared the profiles with transcription changes in human cells subjected to stress conditions. Interestingly, we found an overlap only with the response to treatment with the autophagy inhibitor bafilomycin A1. Finally, we identified 23 genes whose expression is significantly altered in all aneuploids and which may thus serve as aneuploidy markers. Conclusions: Our analysis shows that despite the variability in chromosome content, aneuploidy triggers uniform transcriptional response in human cells. A common response independent of the type of aneuploidy might be exploited as a novel target for cancer therapy. Moreover, the potential aneuploidy markers identified in our analysis might represent novel biomarkers to assess the malignant potential of a tumor.

Weitere Episoden von „Medizin - Open Access LMU - Teil 22/22“

• A cross-sectional analysis of the effects of residential greenness on blood pressure in 10-year old children: results from the GINIplus and LISAplus studies 1. Januar 2014
• A large kindred of pulmonary fibrosis associated with a novel ABCA3 gene variant 1. Januar 2014
• A randomised multicentre trial of acupuncture in patients with seasonal allergic rhinitis - trial intervention including physician and treatment characteristics 1. Januar 2014
• Association between anemia and falls in community-dwelling older people: cross-sectional results from the KORA-Age study 1. Januar 2014
• Biological health or lived health: which predicts self-reported general health better? 1. Januar 2014
• Circulating cell-free methylated DNA and lactate dehydrogenase release in colorectal cancer 1. Januar 2014
• Comparative cost-effectiveness analyses of cardiovascular magnetic resonance and coronary angiography combined with fractional flow reserve for the diagnosis of coronary artery disease 1. Januar 2014
• Comprehensive analysis of beta-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/beta-catenin signaling 1. Januar 2014
• Contribution of socioeconomic status, stature and birth weight to obesity in Sub-Saharan Africa: cross-sectional data from primary school-age children in Cameroon 1. Januar 2014
• Early versus later response to treatment in patients with community-acquired pneumonia: analysis of the REACH study 1. Januar 2014
• Evidence-based decision-making in infectious diseases epidemiology, prevention and control: matching research questions to study designs and quality appraisal tools 1. Januar 2014
• Evidence for significant influence of host immunity on changes in differential blood count during malaria 1. Januar 2014
• Experience of gratitude, awe and beauty in life among patients with multiple sclerosis and psychiatric disorders 1. Januar 2014
• Exploring patterns of accelerometry-assessed physical activity in elderly people 1. Januar 2014
• A comprehensive analysis of Helicobacter pylori plasticity zones reveals that they are integrating conjugative elements with intermediate integration specificity 1. Januar 2014

Alle Episoden von Medizin - Open Access LMU - Teil 22/22 · Mehr Bildung-Podcasts