Three-dimensional nanoscale nuclear architecture mapping for improved cancer risk stratification

Author(s):  
Shikhar Uttam ◽  
Yang Liu
1987 ◽  
Vol 104 (6) ◽  
pp. 1455-1470 ◽  
Author(s):  
M Hochstrasser ◽  
J W Sedat

Interphase chromosome organization in four different Drosophila melanogaster tissues, covering three to four levels of polyteny, has been analyzed. The results are based primarily on three-dimensional reconstructions from unfixed tissues using a computer-based data collection and modeling system. A characteristic organization of chromosomes in each cell type is observed, independent of polyteny, with some packing motifs common to several or all tissues and others tissue-specific. All chromosomes display a right-handed coiling chirality, despite large differences in size and degree of coiling. Conversely, in each cell type, the heterochromatic centromeric regions have a unique structure, tendency to associate, and intranuclear location. The organization of condensed nucleolar chromatin is also tissue-specific. The tightly coiled prothoracic gland chromosomes are arrayed in a similar fashion to the much larger salivary gland chromosomes described previously, having polarized orientations, nonintertwined spatial domains, and close packing of the arms of each autosome, whereas hindgut and especially the unusually straight midgut chromosomes display striking departures from these regularities. Surprisingly, gut chromosomes often appear to be broken in the centric heterochromatin. Severe deformations of midgut nuclei observed during gut contractions in living larvae may account for their unusual properties. Finally, morphometric measurements of chromosome and nuclear dimensions provide insights into chromosome growth and substructure and also suggest an unexpected parallel with diploid chromatin organization.


2018 ◽  
Vol 7 (S4) ◽  
pp. S443-S452 ◽  
Author(s):  
Nachiketh Soodana-Prakash ◽  
Radka Stoyanova ◽  
Abhishek Bhat ◽  
Maria C. Velasquez ◽  
Omer E. Kineish ◽  
...  

2012 ◽  
Vol 6 (2) ◽  
Author(s):  
George Rodrigues ◽  
Padraig Warde ◽  
Tom Pickles ◽  
Juanita Crook ◽  
Michael Brundage ◽  
...  

Introduction:  The use of accepted prostate cancer risk stratification groups based on prostate-specific antigen, T stage and Gleason score assists in therapeutic treatment decision-making, clinical trial design and outcome reporting. The utility of integrating novel prognostic factors into an updated risk stratification schema is an area of current debate. The purpose of this work is to critically review the available literature on novel pre-treatment prognostic factors and alternative prostate cancer risk stratification schema to assess the feasibility and need for changes to existing risk stratification systems. Methods:  A systematic literature search was conducted to identify original research publications and review articles on prognostic factors and risk stratification in prostate cancer. Search terms included risk stratification, risk assessment, prostate cancer or neoplasms, and prognostic factors. Abstracted information was assessed to draw conclusions regarding the potential utility of changes to existing risk stratification schema. Results:  The critical review identified three specific clinically relevant potential changes to the most commonly used three-group risk stratification system: (1) the creation of a very-low risk category; (2) the splitting of intermediate-risk into a low- and highintermediate risk groups; and (3) the clarification of the interface between intermediate- and high-risk disease. Novel pathological factors regarding high-grade cancer, subtypes of Gleason score 7 and percentage biopsy cores positive were also identified as potentially important risk-stratification factors. Conclusions:  Multiple studies of prognostic factors have been performed to create currently utilized prostate cancer risk stratification systems. We propose potential changes to existing systems.


2018 ◽  
Vol 27 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Hiroaki Harada ◽  
Kazuaki Miyamaoto ◽  
Masami Kimura ◽  
Tetsuro Ishigami ◽  
Kiyomi Taniyama ◽  
...  

Background Assuming that the entire airway is affected by the same inhaled carcinogen, similar molecular alterations may occur in the lung and oral cavity. Thus, we hypothesized that DNA methylation profiles in the oral epithelium may be a promising biomarker for lung cancer risk stratification. Methods A methylation-specific polymerase chain reaction was performed on oral epithelium from 16 patients with lung cancer and 32 controls without lung cancer. Genes showing aberrant methylation profiles in the oral epithelium were compared between patients and controls. Results The analysis revealed that HOXD11 and PCDHGB6 were methylated more frequently in patients than in controls ( p = 0.0055 and p = 0.0247, respectively). Combined analyses indicated that 8 of 16 (50%) patients and 3 of 32 (9.4%) controls showed DNA methylation in both genes ( p = 0.0016). Among the population limited to current and former smokers, 6 of 11 (54.5%) patients showed methylation in both genes, compared to 1 of 17 (5.9%) controls ( p = 0.0037). In a subgroup analysis limited to the population above 50-years old, 8 of 16 (50%) patients and 2 of 16 (12.5%) controls showed methylation in both genes ( p = 0.0221). Conclusions The results of this study indicate that specific gene methylation in the oral epithelium might be a promising biomarker for lung cancer risk assessment, especially among smokers. Risk stratification through the analysis of DNA methylation profiles in the oral epithelium may be a useful and less invasive first-step approach in an efficient two-step lung cancer screening strategy.


2019 ◽  
Author(s):  
Ailish Gallagher ◽  
Jo Waller ◽  
Ranjit Manchanda ◽  
Ian Jacobs ◽  
Saskia Sanderson

Risk stratification using genetic and/or other types of information could identify women at increased ovarian cancer risk. The aim of this study was to examine women’s potential reactions to ovarian cancer risk stratification. 1,017 women aged 45-75 years took part in an online experimental survey. Women were randomly assigned to one of three experimental conditions describing hypothetical personal results from ovarian cancer risk stratification, and asked to imagine they had received one of three results: (a) 5% risk due to SNPs and lifestyle factors; (b) 10% risk due to SNPs and lifestyle factors; (c) 10% risk due to a rare mutation in BRCA2. 83% of women indicated interest in having ovarian cancer risk assessment. After receiving their hypothetical risk estimates, 29% of women stated they would have risk-reducing surgery. Choosing risk-reducing surgery over other behavioural responses was associated with having higher surgery self-efficacy and perceived response-efficacy, but not with perceptions of disease threat, i.e. perceived risk or severity, or with experimental condition. A substantial proportion of women age 45-75 years may be open to the idea of surgery to reduce risk of ovarian cancer, even if their absolute lifetime risk is only increased to as little as 5 or 10%.


2021 ◽  
pp. 137-151
Author(s):  
Rohit Rastogi ◽  
Mukund Rastogi ◽  
D. K. Chaturvedi ◽  
Sheelu Sagar ◽  
Neeti Tandon

2019 ◽  
Vol 40 (1) ◽  
Author(s):  
Svetlana Puzhko ◽  
Justin Gagnon ◽  
Jacques Simard ◽  
Bartha Maria Knoppers ◽  
Sophia Siedlikowski ◽  
...  

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