scholarly journals Cis-regulatory Element Hijacking Overshadows Topological Changes in Prostate Cancer

2021 ◽  
Author(s):  
James R. Hawley ◽  
Stanley Zhou ◽  
Christopher Arlidge ◽  
Giacomo Grillo ◽  
Ken Kron ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Large Scale ◽  
Genome Instability ◽  
Regulatory Element ◽  
Three Dimensional ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Structural Variants ◽  
The Impact ◽  
Topological Changes

AbstractProstate cancer is a heterogeneous disease whose progression is linked to genome instability 1. Despite large-scale tumour sequencing efforts, the impact of mutations on the genetic architecture in cancer remains ill-defined due to limited integration of genomics data across dimensions 2. We addressed this limitation by assessing the impact of structural variants on the chromatin states and the three-dimensional organization across benign and malignant primary prostate genomes. We find high concordance in the three-dimensional genome organization between malignant and benign prostate tissues, arguing for constraints to the three-dimensional genome of prostate tumours. Moreover, we identify structural variants as effectors of changes to focal chromatin interactions, guiding cis-regulatory element hijacking 2,3 that imposes opposing expression changes on genes found at antipodes of a rearrangement. This leads to the repression of tumour suppressor gene expression and up-regulation of oncogenes, such as at the TMPRSS2-ERG and PMEPA1-ZNF156 loci. Collectively, our results argue that cis-regulatory element hijacking by structural variants overshadows large-scale topological changes to alter gene regulation and promote oncogenesis.

scholarly journals 3DIV update for 2021: a comprehensive resource of 3D genome and 3D cancer genome

2020 ◽  
Vol 49 (D1) ◽  
pp. D38-D46
Author(s):  
Kyukwang Kim ◽  
Insu Jang ◽  
Mooyoung Kim ◽  
Jinhyuk Choi ◽  
Min-Seo Kim ◽  
...  
Keyword(s):  
Cell Line ◽  
Large Scale ◽  
Three Dimensional ◽  
Cancer Cell Line ◽  
Cancer Genome ◽  
Structural Variations ◽  
3D Genome ◽  
Tightly Coupled ◽  
Regulatory Effects ◽  
The Impact

Abstract Three-dimensional (3D) genome organization is tightly coupled with gene regulation in various biological processes and diseases. In cancer, various types of large-scale genomic rearrangements can disrupt the 3D genome, leading to oncogenic gene expression. However, unraveling the pathogenicity of the 3D cancer genome remains a challenge since closer examinations have been greatly limited due to the lack of appropriate tools specialized for disorganized higher-order chromatin structure. Here, we updated a 3D-genome Interaction Viewer and database named 3DIV by uniformly processing ∼230 billion raw Hi-C reads to expand our contents to the 3D cancer genome. The updates of 3DIV are listed as follows: (i) the collection of 401 samples including 220 cancer cell line/tumor Hi-C data, 153 normal cell line/tissue Hi-C data, and 28 promoter capture Hi-C data, (ii) the live interactive manipulation of the 3D cancer genome to simulate the impact of structural variations and (iii) the reconstruction of Hi-C contact maps by user-defined chromosome order to investigate the 3D genome of the complex genomic rearrangement. In summary, the updated 3DIV will be the most comprehensive resource to explore the gene regulatory effects of both the normal and cancer 3D genome. ‘3DIV’ is freely available at http://3div.kr.

scholarly journals Genetic Variants of DICE1/INTS6 in German Prostate Cancer Families with Linkage to 13q14

2015 ◽  
Vol 95 (4) ◽  
pp. 386-389 ◽  
Author(s):  
Malte Böhm ◽  
Christiane Maier ◽  
Rainer Küfer ◽  
Albrecht Röpke ◽  
Walther Vogel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Genetic Basis ◽  
Cancer Susceptibility ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Caucasian Men ◽  
Chromosome 13Q14 ◽  
Exon 10

Introduction: Prostate cancer is the most frequent malignancy found to occur in Caucasian men, but its genetic basis remains elusive. A prostate cancer-susceptibility locus has been identified on chromosome 13q14. The tumour suppressor gene deleted in cancer cells 1 (DICE1/INTS6) is located within this interval on 13q14.3. Materials and Methods: We performed mutation analysis of the DICE1/INTS6 gene in thirteen German prostate cancer families. Results and Conclusion: None of the patients harboured DICE1 mutations, and similar frequencies of the previously identified 13 bp deletion polymorphism in the DICE1 promoter were observed in the familial prostate cancer patients as compared with sporadic prostate cancer patients and controls. However, in one family with three affected brothers, the variations c.1215A>C (p.T405T) in exon 10 and c.2568A>G (p.S856S) in exon 17 were detected in a heterozygous pattern. In sporadic prostate cancer patients, variant c.2568A>G (p.S856S) was detected in 10/325 (3.08%) compared with 5/207 (2.42%) control samples (p > 0.05). We conclude that DICE1 appears to be involved in prostate cancer progression rather than in the initiation of prostate cancer.

scholarly journals Altered topology of large-scale structural brain networks in chronic stroke

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Bastian Cheng ◽  
Eckhard Schlemm ◽  
Robert Schulz ◽  
Marlene Boenstrup ◽  
Arnaud Messé ◽  
...  
Keyword(s):  
Information Transfer ◽  
Large Scale ◽  
Neuronal Degeneration ◽  
Brain Networks ◽  
Brain Regions ◽  
Local Network ◽  
Structural Connectome ◽  
The Impact ◽  
Structural Brain ◽  
Topological Changes

Abstract Beyond disruption of neuronal pathways, focal stroke lesions induce structural disintegration of distant, yet connected brain regions via retrograde neuronal degeneration. Stroke lesions alter functional brain connectivity and topology in large-scale brain networks. These changes are associated with the degree of clinical impairment and recovery. In contrast, changes of large scale, structural brain networks after stroke are less well reported. We therefore aimed to analyse the impact of focal lesions on the structural connectome after stroke based on data from diffusion-weighted imaging and probabilistic fibre tracking. In total, 17 patients (mean age 64.5 ± 8.4 years) with upper limb motor deficits in the chronic stage after stroke and 21 healthy participants (mean age 64.9 ± 10.3 years) were included. Clinical deficits were evaluated by grip strength and the upper extremity Fugl-Meyer assessment. We calculated global and local graph theoretical measures to characterize topological changes in the structural connectome. Results from our analysis demonstrated significant alterations of network topology in both ipsi- and contralesional, primarily unaffected, hemispheres after stroke. Global efficiency was significantly lower in stroke connectomes as an indicator of overall reduced capacity for information transfer between distant brain areas. Furthermore, topology of structural connectomes was shifted toward a higher degree of segregation as indicated by significantly higher values of global clustering and modularity. On a level of local network parameters, these effects were most pronounced in a subnetwork of cortico-subcortical brain regions involved in motor control. Structural changes were not significantly associated with clinical measures. We propose that the observed network changes in our patients are best explained by the disruption of inter- and intrahemispheric, long white matter fibre tracts connecting distant brain regions. Our results add novel insights on topological changes of structural large-scale brain networks in the ipsi- and contralesional hemisphere after stroke.

scholarly journals Strategies to evaluate the impact of rectal volume on prostate motion during three-dimensional conformal radiotherapy for prostate cancer

2016 ◽  
Vol 49 (1) ◽  
pp. 17-20 ◽  
Author(s):  
Ana Paula Diniz Fortuna Poli ◽  
Rodrigo Souza Dias ◽  
Adelmo José Giordani ◽  
Helena Regina Comodo Segreto ◽  
Roberto Araujo Segreto
Keyword(s):  
Prostate Cancer ◽  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
Prostate Motion ◽  
Rectal Volume ◽  
Three Dimensional Conformal Radiotherapy ◽  
Interfraction Motion ◽  
The Impact ◽  
Anterior Posterior ◽  
3D Crt

Abstract Objective: To evaluate the rectal volume influence on prostate motion during three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Materials and Methods: Fifty-one patients with prostate cancer underwent a series of three computed tomography scans including an initial planning scan and two subsequent scans during 3D-CRT. The organs of interest were outlined. The prostate contour was compared with the initial CT images considering the anterior, posterior, superior, inferior and lateral edges of the organ. Variations in the anterior limits and volume of the rectum were assessed and correlated with prostate motion in the anteroposterior direction. Results: The maximum range of prostate motion was observed in the superoinferior direction, followed by the anteroposterior direction. A significant correlation was observed between prostate motion and rectal volume variation ( p = 0.037). A baseline rectal volume superior to 70 cm3 had a significant influence on the prostate motion in the anteroposterior direction ( p = 0.045). Conclusion: The present study showed a significant interfraction motion of the prostate during 3D-CRT with greatest variations in the superoinferior and anteroposterior directions, and that a large rectal volume influences the prostate motion with a cutoff value of 70 cm3. Therefore, the treatment of patients with a rectal volume > 70 cm3 should be re-planned with appropriate rectal preparation.

p53 Tumour Suppressor Gene Mutations in Benign Prostatic Hyperplasia and Prostate Cancer

1998 ◽  
Vol 34 (5) ◽  
pp. 433-440 ◽  
Author(s):  
Horst Schlechte ◽  
Severin V. Lenk ◽  
Thomas Löning ◽  
Dietmar Schnorr ◽  
Birgit D. Rudolph ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Gene Mutations ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Prostatic Hyperplasia ◽  
Tumour Suppressor ◽  
P53 Tumour Suppressor Gene

Can the Deforestation Breeze Change the Rainfall in Amazonia? A Case Study for the BR-163 Highway Region

2010 ◽  
Vol 14 (18) ◽  
pp. 1-25 ◽  
Author(s):  
Sandra I. Saad ◽  
Humberto R. da Rocha ◽  
Maria A. F. Silva Dias ◽  
Rafael Rosolem
Keyword(s):  
Boundary Layer ◽  
Large Scale ◽  
Three Dimensional ◽  
Atmospheric Modeling ◽  
Thermal Cell ◽  
Soil Wetness ◽  
Soil Dryness ◽  
Regional Atmospheric Modeling ◽  
The Impact

Abstract The authors simulated the effects of Amazonian mesoscale deforestation in the boundary layer and in rainfall with the Brazilian Regional Atmospheric Modeling System (BRAMS) model. They found that both the area and shape (with respect to wind incidence) of deforestation and the soil moisture status contributed to the state of the atmosphere during the time scale of several weeks, with distinguishable patterns of temperature, humidity, and rainfall. Deforestation resulted in the development of a three-dimensional thermal cell, the so-called deforestation breeze, slightly shifted downwind to large-scale circulation. The boundary layer was warmer and drier above 1000-m height and was slightly wetter up to 2000-m height. Soil wetness affected the circulation energetics proportionally to the soil dryness (for soil wetness below ∼0.6). The shape of the deforestation controlled the impact on rainfall. The horizontal strips lined up with the prevailing wind showed a dominant increase in rainfall, significant up to about 60 000 km2. On the other hand, in the patches aligned in the opposite direction (north–south), there was both increase and decrease in precipitation in two distinct regions, as a result of clearly separated upward and downward branches, which caused the precipitation to increase for patches up to 15 000 km2. The authors’ estimates for the size of deforestation impacting the rainfall contributed to fill up the low spatial resolution in other previous studies.

An Impact Assessment of GPS Radio Occultation Data on Prediction of a Rapidly Developing Cyclone over the Southern Ocean*

2014 ◽  
Vol 142 (11) ◽  
pp. 4187-4206 ◽  
Author(s):  
Shu-Ya Chen ◽  
Tae-Kwon Wee ◽  
Ying-Hwa Kuo ◽  
David H. Bromwich
Keyword(s):  
Data Assimilation ◽  
Southern Ocean ◽  
Large Scale ◽  
Radio Occultation ◽  
Three Dimensional ◽  
Wrf Model ◽  
The Other ◽  
Gps Radio Occultation ◽  
The Antarctic ◽  
The Impact

Abstract The impact of global positioning system (GPS) radio occultation (RO) data on an intense synoptic-scale storm that occurred over the Southern Ocean in December 2007 is evaluated, and a synoptic explanation of the assessed impact is offered. The impact is assessed by using the three-dimensional variational data assimilation scheme (3DVAR) of the Weather Research and Forecasting (WRF) Model Data Assimilation system (WRFDA), and by comparing two experiments: one with and the other without assimilating the refractivity data from four different RO missions. Verifications indicate significant positive impacts of the RO data in various measures and parameters as well as in the track and intensity of the Antarctic cyclone. The analysis of the atmospheric processes underlying the impact shows that the assimilation of the RO data yields substantial improvements in the large-scale circulations that in turn control the development of the Antarctic storm. For instance, the RO data enhanced the strength of a 500-hPa trough over the Southern Ocean and prevented the katabatic flow near the coast of East Antarctica from an overintensification. This greatly influenced two low pressure systems of a comparable intensity, which later merged together and evolved into the major storm. The dominance of one low over the other in the merger dramatically changed the track, intensity, and structure of the merged storm. The assimilation of GPS RO data swapped the dominant low, leading to a remarkable improvement in the subsequent storm’s prediction.

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