scholarly journals Association between mRNA expression of chemotherapy-related genes and clinicopathological features in colorectal cancer: A large-scale population analysis

2015 ◽  
Vol 37 (2) ◽  
pp. 319-328 ◽  
Author(s):  
YUJI SHIMAMOTO ◽  
MAMORU NUKATSUKA ◽  
TEIJI TAKECHI ◽  
MASAKAZU FUKUSHIMA
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Large Scale ◽  
Population Analysis ◽  
Clinicopathological Features ◽  
Scale Population

Clinicopathological features of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) in Japanese patients.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 629-629
Author(s):  
Akihito Kawazoe ◽  
Kohei Shitara ◽  
Masaaki Noguchi ◽  
Shota Fukuoka ◽  
Yasutoshi Kuboki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Microsatellite Instability ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Large Scale ◽  
Phase Ii Trial ◽  
Japanese Patients ◽  
Clinicopathological Features ◽  
Braf V600e

629 Background: Recently, anti-programmed death 1 (PD-1) antibody has shown promising efficacy in a phase II trial for patients with microsatellite instability-high (MSI-H) tumors, especially in those with metastatic colorectal cancer (mCRC). Currently, several clinical trials of anti-PD-1 antibody for patients with MSI-H mCRC are ongoing. However, little is known about the frequencies and clinicopathological features of MSI-H mCRC in Japanese patients. Methods: Patients with histologically confirmed adenocarcinoma of mCRC were eligible for this observational study. MSI status was analyzed in tumors using the MSI Analysis System (Promega) composed of 5 mononucleotide markers. KRAS, NRAS, BRAF and PIK3CA mutations were also evaluated using the multiplex kit. Results: A total of 232 patients were enrolled until August 31, 2015, of which MSI-H was detected in 5 patients (2.1%). Among five patients with MSI-H mCRC, median age was 45 years (28-75), four had tumors on right-sided colon, five had moderately differentiated adenocarcinoma, one had poorly differentiated adenocarcinoma, and three had stage IV disease at presentation. Overall survival for patients with MSI-H mCRC from the start of first-line systemic chemotherapy ranged from 8.1 to 62.0 month. All five patients with MSI-H mCRC had RAS wild-type tumors and two had BRAF V600E mutation. One patient with MSI-H mCRC was enrolled in a phase II trial of anti-PD-1 antibody. Conclusions: MSI-H mCRC is rare in Japanese patients. A large scale nationwide cancer genome screening project together with MSI status is required to evaluate more detailed clinicopathological features and facilitate the enrollment of patients with MSI-H mCRC for clinical trials with anti-PD-1 antibody.

scholarly journals Population analysis of retrotransposons in giraffe genomes supports RTE decline and widespread LINE1 activity in Giraffidae

Mobile DNA ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Malte Petersen ◽  
Sven Winter ◽  
Raphael Coimbra ◽  
Menno J. de Jong ◽  
Vladimir V. Kapitonov ◽  
...  
Keyword(s):  
Large Scale ◽  
Population Analysis ◽  
Model Organism ◽  
Population Level ◽  
Data Sets ◽  
Ltr Retrotransposons ◽  
Scale Population ◽  
Mammalian Genomes ◽  
Genome Assemblies ◽  
First Time

Abstract Background The majority of structural variation in genomes is caused by insertions of transposable elements (TEs). In mammalian genomes, the main TE fraction is made up of autonomous and non-autonomous non-LTR retrotransposons commonly known as LINEs and SINEs (Long and Short Interspersed Nuclear Elements). Here we present one of the first population-level analysis of TE insertions in a non-model organism, the giraffe. Giraffes are ruminant artiodactyls, one of the few mammalian groups with genomes that are colonized by putatively active LINEs of two different clades of non-LTR retrotransposons, namely the LINE1 and RTE/BovB LINEs as well as their associated SINEs. We analyzed TE insertions of both types, and their associated SINEs in three giraffe genome assemblies, as well as across a population level sampling of 48 individuals covering all extant giraffe species. Results The comparative genome screen identified 139,525 recent LINE1 and RTE insertions in the sampled giraffe population. The analysis revealed a drastically reduced RTE activity in giraffes, whereas LINE1 is still actively propagating in the genomes of extant (sub)-species. In concert with the extremely low activity of the giraffe RTE, we also found that RTE-dependent SINEs, namely Bov-tA and Bov-A2, have been virtually immobile in the last 2 million years. Despite the high current activity of the giraffe LINE1, we did not find evidence for the presence of currently active LINE1-dependent SINEs. TE insertion heterozygosity rates differ among the different (sub)-species, likely due to divergent population histories. Conclusions The horizontally transferred RTE/BovB and its derived SINEs appear to be close to inactivation and subsequent extinction in the genomes of extant giraffe species. This is the first time that the decline of a TE family has been meticulously analyzed from a population genetics perspective. Our study shows how detailed information about past and present TE activity can be obtained by analyzing large-scale population-level genomic data sets.

scholarly journals Large-scale population analysis of SARS-CoV-2 whole genome sequences reveals host-mediated viral evolution with emergence of mutations in the viral Spike protein associated with elevated mortality rates

2020 ◽  
Author(s):  
Carlos Farkas ◽  
Andy Mella ◽  
Jody J. Haigh
Keyword(s):  
Large Scale ◽  
Population Analysis ◽  
Viral Evolution ◽  
Population Level ◽  
Spike Protein ◽  
Host Immune System ◽  
Sequencing Data ◽  
Scale Population ◽  
Significant Public Health ◽  
Viral Sequences

AbstractBackgroundWe aimed to further characterize and analyze in depth intra-host variation and founder variants of SARS-CoV-2 worldwide up until August 2020, by examining in excess of 94,000 SARS-CoV-2 viral sequences in order to understand SARS-CoV-2 variant evolution, how these variants arose and identify any increased mortality associated with these variants.Methods and FindingsWe combined worldwide sequencing data from GISAID and Sequence Read Archive (SRA) repositories and discovered SARS-CoV-2 hypermutation occurring in less than 2% of COVID19 patients, likely caused by host mechanisms involved APOBEC3G complexes and intra-host microdiversity. Most of this intra-host variation occurring in SARS-CoV-2 are predicted to change viral proteins with defined variant signatures, demonstrating that SARS-CoV-2 can be actively shaped by the host immune system to varying degrees. At the global population level, several SARS-CoV-2 proteins such as Nsp2, 3C-like proteinase, ORF3a and ORF8 are under active evolution, as evidenced by their increased πN/πS ratios per geographical region. Importantly, two emergent variants: V1176F in co-occurrence with D614G mutation in the viral Spike protein, and S477N, located in the Receptor Binding Domain (RBD) of the Spike protein, are associated with high fatality rates and are increasingly spreading throughout the world. The S477N variant arose quickly in Australia and experimental data support that this variant increases Spike protein fitness and its binding to ACE2.ConclusionsSARS-CoV-2 is evolving non-randomly, and human hosts shape emergent variants with positive fitness that can easily spread into the population. We propose that V1776F and S477N variants occurring in the Spike protein are two novel mutations occurring in SARS-CoV-2 and may pose significant public health concerns in the future.

scholarly journals Large-Scale Population Analysis Challenges the Current Criteria for the Molecular Diagnosis of Fascioscapulohumeral Muscular Dystrophy

2012 ◽  
Vol 90 (4) ◽  
pp. 628-635 ◽  
Author(s):  
Isabella Scionti ◽  
Francesca Greco ◽  
Giulia Ricci ◽  
Monica Govi ◽  
Patricia Arashiro ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Molecular Diagnosis ◽  
Large Scale ◽  
Population Analysis ◽  
Scale Population

scholarly journals Rapid Population Analysis of Magnaporthe grisea by Using rep-PCR and Endogenous Repetitive DNA Sequences

1998 ◽  
Vol 88 (3) ◽  
pp. 223-229 ◽  
Author(s):  
M. L. C. George ◽  
R. J. Nelson ◽  
R. S. Zeigler ◽  
H. Leung
Keyword(s):  
Dna Sequences ◽  
Large Scale ◽  
Magnaporthe Grisea ◽  
Population Analysis ◽  
Low Cost ◽  
Genetic Relationships ◽  
Fungal Genome ◽  
Scale Population ◽  
Polymerase Chain ◽  
The Impact

DNA samples from Magnaporthe grisea isolates were fingerprinted by using repetitive element-based polymerase chain reaction (rep-PCR) with two outwardly directed primer sequences from Pot2, an element found in approximately 100 copies in the fungal genome. Variable length fragments, defining the sequences lying between these elements, were generated, and fingerprint patterns specific for individual strains were established. “Long PCR” conditions, including higher pH (9.2) and increased extension time (10 min) were used to amplify DNA fragments ranging from 400 bp to longer than 23 kb. Polymorphisms specific to M. grisea strains were generated, allowing inference of their genetic relationships. Segregation analysis was used to confirm single-locus inheritance for the fragments amplified by rep-PCR. Cluster analysis revealed robust groupings that corresponded to previously determined MGR586 restriction fragment length polymorphism lineages of the rice-infecting strains of the pathogen. We have also demonstrated the utility of rep-PCR to differentiate isolates that infect rice from those that infect nonrice hosts. DNA fingerprinting by Pot2 rep-PCR provides an efficient means to monitor the population dynamics of the blast pathogen. Because of the method's low cost and ease in application, it is now feasible to conduct large-scale population studies to understand the impact of host genotypes on pathogen evolution.

scholarly journals Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis

2021 ◽  
Author(s):  
Richard Culliford ◽  
Alex J. Cornish ◽  
Philip J. Law ◽  
Susan M. Farrington ◽  
Kimmo Palin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Large Scale ◽  
Causal Effect ◽  
Gallstone Disease ◽  
Epidemiological Studies ◽  
Mendelian Randomisation ◽  
Linear Relationships ◽  
Potential Risk Factors ◽  
The Relationship ◽  
Circulating Levels

Abstract Background Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR). Methods We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (ORSD) for CRC and tested for a non-zero causal effect of gallstones on CRC. Sensitivity analysis was applied to identify violations of estimator assumptions. Results No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (ORSD = 1.00, 95% confidence interval (CI) = 0.96–1.03, P value = 0.90) with CRC was shown. Conclusions Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.

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