scholarly journals PTEN Protein losses and loss-of-function genetic variants in gastric cancers: the relationship with microsatellite instability, EBV, and PD-L1 expression

Pathology ◽  
2020 ◽  
Vol 52 ◽  
pp. S120
Author(s):  
Binnari Kim ◽  
So Young Kang ◽  
Deokgeun Kim ◽  
Eun Ji Kim ◽  
You Jeong Heo ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Genetic Variants ◽  
Loss Of Function ◽  
Pten Protein ◽  
Gastric Cancers ◽  
The Relationship

scholarly journals PTEN Protein Loss and Loss-of-Function Mutations in Gastric Cancers: The Relationship with Microsatellite Instability, EBV, HER2, and PD-L1 Expression

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1724
Author(s):  
Binnari Kim ◽  
So Young Kang ◽  
Deokgeun Kim ◽  
You Jeong Heo ◽  
Kyoung-Mee Kim
Keyword(s):  
Protein Expression ◽  
Microsatellite Instability ◽  
Genetic Alterations ◽  
Her2 Overexpression ◽  
Nuclear Staining ◽  
Loss Of Function ◽  
Protein Loss ◽  
Pten Protein ◽  
Barr Virus ◽  
The Relationship

Inactivation of phosphatase and tensin homolog (PTEN) is caused by multiple mechanisms, and loss of PTEN activity is related to the progression of various cancers. In gastric cancer (GC), the relationship between the loss of PTEN protein expression and various genetic alterations remains unclear. The effects of microsatellite instability (MSI), Epstein–Barr virus (EBV), HER2 overexpression, and PD-L1 expression on PTEN mutation have not been fully explored. We performed comprehensive cancer panel tests with a cohort of 322 tumor samples from patients with advanced GC. Immunohistochemistry for PTEN protein was performed in all cases, and the loss of protein expression was defined as a complete absence of nuclear staining. In total, 34 cases (10.6%) had pathogenic PTEN mutations, of which 19 (55.9%) showed PTEN protein loss. The most common PTEN variants associated with protein loss were p.R130 (n = 4) followed by p.R335, p.L265fs, and deletions (n = 2). All the ten nonsense mutations identified in the samples resulted in PTEN inactivation. In the remaining 288 GC cases with wild-type PTEN, protein loss was found in 35 cases (12.2%). Thus, PTEN mutations were significantly associated with PTEN protein loss (p = 5.232 × 10−10), high MSI (p = 3.936 × 10−8), and EBV-positivity (p = 0.0071). In conclusion, our results demonstrate that loss-of-function mutations in PTEN are a frequent genetic mechanism of PTEN inactivation in GC.

Migraine: Genetic Variants and Clinical Phenotypes

2019 ◽  
Vol 26 (34) ◽  
pp. 6207-6221 ◽  
Author(s):  
Innocenzo Rainero ◽  
Alessandro Vacca ◽  
Flora Govone ◽  
Annalisa Gai ◽  
Lorenzo Pinessi ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Mthfr Gene ◽  
Genome Wide Association Studies ◽  
Clinical Phenotypes ◽  
Network Analyses ◽  
Genome Wide ◽  
Genomic Studies ◽  
The Common ◽  
The Relationship

Migraine is a common, chronic neurovascular disorder caused by a complex interaction between genetic and environmental risk factors. In the last two decades, molecular genetics of migraine have been intensively investigated. In a few cases, migraine is transmitted as a monogenic disorder, and the disease phenotype cosegregates with mutations in different genes like CACNA1A, ATP1A2, SCN1A, KCNK18, and NOTCH3. In the common forms of migraine, candidate genes as well as genome-wide association studies have shown that a large number of genetic variants may increase the risk of developing migraine. At present, few studies investigated the genotype-phenotype correlation in patients with migraine. The purpose of this review was to discuss recent studies investigating the relationship between different genetic variants and the clinical characteristics of migraine. Analysis of genotype-phenotype correlations in migraineurs is complicated by several confounding factors and, to date, only polymorphisms of the MTHFR gene have been shown to have an effect on migraine phenotype. Additional genomic studies and network analyses are needed to clarify the complex pathways underlying migraine and its clinical phenotypes.

Microsatellite Instability and K-ras Mutations in Gastric Adenomas, with Reference to Associated Gastric Cancers

1999 ◽  
Vol 23 (3) ◽  
pp. 204-214 ◽  
Author(s):  
Jun Isogaki ◽  
Kazuya Shinmura ◽  
Wang Yin ◽  
Tomio Arai ◽  
Kenji Koda ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Ras Mutations ◽  
Gastric Cancers

THE RELATIONSHIP BETWEEN OBSTRUCTIVE SLEEP APNOEA AND TASK-1 GENETIC VARIANTS

2018 ◽  
Vol 36 (Supplement 1) ◽  
pp. e205
Author(s):  
N. Li ◽  
T. Shi ◽  
X. Yao ◽  
Y. Wang ◽  
M. Heizhati ◽  
...  
Keyword(s):  
Obstructive Sleep Apnoea ◽  
Genetic Variants ◽  
Sleep Apnoea ◽  
Obstructive Sleep ◽  
The Relationship ◽  
And Task

Studying how genetic variants affect mechanism in biological systems

2018 ◽  
Vol 62 (4) ◽  
pp. 575-582
Author(s):  
Francesco Raimondi ◽  
Robert B. Russell
Keyword(s):  
Genetic Variation ◽  
Molecular Mechanism ◽  
Genetic Variants ◽  
Biological Function ◽  
Biological Systems ◽  
Protein Structures ◽  
Clinical Applications ◽  
Biological Pathways ◽  
The Relationship

Genetic variants are currently a major component of system-wide investigations into biological function or disease. Approaches to select variants (often out of thousands of candidates) that are responsible for a particular phenomenon have many clinical applications and can help illuminate differences between individuals. Selecting meaningful variants is greatly aided by integration with information about molecular mechanism, whether known from protein structures or interactions or biological pathways. In this review we discuss the nature of genetic variants, and recent studies highlighting what is currently known about the relationship between genetic variation, biomolecular function, and disease.

scholarly journals THE RELATIONSHIP BETWEEN GENETIC VARIANTS OF B-LACTOGLOBULIN AND K-CASEIN AND SELECTED PARAMETERS OF THE SUITABILITY OF MILK FOR CHEESE PRODUCTION

2016 ◽  
Vol 15 (3) ◽  
pp. 53-66
Author(s):  
Anna Wolanciuk ◽  
◽  
Joanna Barłowska ◽  
Zygmunt Litwińczuk ◽  
Wioletta Sawicka-Zugaj ◽  
...  
Keyword(s):  
Genetic Variants ◽  
The Relationship ◽  
Cheese Production

scholarly journals Genetic Diversity and Evolution of the Biological Features of the Pandemic SARS-CoV-2

Acta Naturae ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 77-89
Author(s):  
Aleksandra A. Nikonova ◽  
Eugene B. Faizuloev ◽  
Anastasia V. Gracheva ◽  
Igor Yu. Isakov ◽  
Vitaly V. Zverev
Keyword(s):  
Genetic Diversity ◽  
Genetic Variants ◽  
Large Scale ◽  
Biological Properties ◽  
Viral Genomes ◽  
Biological Features ◽  
Health Measures ◽  
Common Genetic Variants ◽  
Coronavirus Infection ◽  
The Relationship

The new coronavirus infection (COVID-19) represents a challenge for global health. Since the outbreak began, the number of confirmed cases has exceeded 117 million, with more than 2.6 million deaths worldwide. With public health measures aimed at containing the spread of the disease, several countries have faced a crisis in the availability of intensive care units. Currently, a large-scale effort is underway to identify the nucleotide sequences of the SARS-CoV-2 coronavirus that is an etiological agent of COVID-19. Global sequencing of thousands of viral genomes has revealed many common genetic variants, which enables the monitoring of the evolution of SARS-CoV-2 and the tracking of its spread over time. Understanding the current evolution of SARS-CoV-2 is necessary not only for a retrospective analysis of the new coronavirus infection spread, but also for the development of approaches to the therapy and prophylaxis of COVID-19. In this review, we have focused on the general characteristics of SARS-CoV-2 and COVID-19. Also, we have analyzed available publications on the genetic diversity of the virus and the relationship between the diversity and the biological properties of SARS-CoV-2, such as virulence and contagiousness.

scholarly journals Identification and validation of novel candidate risk genes in endocytic vesicular trafficking associated with esophageal atresia and tracheoesophageal fistulas

2021 ◽  
Author(s):  
Guojie Zhong ◽  
Priyanka Ahimaz ◽  
Nicole A. Edwards ◽  
Jacob J. Hagen ◽  
Christophe Faure ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Congenital Anomalies ◽  
De Novo ◽  
Simulation Analysis ◽  
Loss Of Function ◽  
Developmental Defects ◽  
Risk Genes ◽  
Significant Burden ◽  
Background Mutation Rate ◽  
Complex Cases

Esophageal atresias/tracheoesophageal fistulas (EA/TEF) are rare congenital anomalies caused by aberrant development of the foregut. Previous studies indicate that rare or de novo genetic variants significantly contribute to EA/TEF risk, and most individuals with EA/TEF do not have pathogenic genetic variants in established risk genes. To identify novel genetic contributions to EA/TEF, we performed whole genome sequencing of 185 trios (probands and parents) with EA/TEF, including 59 isolated and 126 complex cases with additional congenital anomalies and/or neurodevelopmental disorders. There was a significant burden of protein altering de novo coding variants in complex cases (p=3.3e-4), especially in genes that are intolerant of loss of function variants in the population. We performed simulation analysis of pathway enrichment based on background mutation rate and identified a number of pathways related to endocytosis and intracellular trafficking that as a group have a significant burden of protein altering de novo variants. We assessed 18 variants for disease causality using CRISPR-Cas9 mutagenesis in Xenopus and confirmed 13 with tracheoesophageal phenotypes. Our results implicate disruption of endosome-mediated epithelial remodeling as a potential mechanism of foregut developmental defects. This research may have implications for the mechanisms of other rare congenital anomalies.

scholarly journals Elevated METTL9 is associated with peritoneal dissemination in human scirrhous gastric cancers

2021 ◽  
Author(s):  
Toshifumi Hara ◽  
Yuuki Tominaga ◽  
Koji Ueda ◽  
Keichiro Mihara ◽  
Kazuyoshi Yanagihara ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Peritoneal Dissemination ◽  
Migration And Invasion ◽  
Gastric Cancers ◽  
Metastatic Cells ◽  
Metastatic Activity ◽  
Gastric Cancer Patients ◽  
Cellular Components ◽  
Complex I Activity ◽  
The Relationship

Methylation, the most common chemical modification of cellular components such as DNA, RNA, and proteins, impacts biological processes including transcription, RNA processing, and protein dynamics. Although abnormal expression of methyltransferase can lead to various diseases including cancers, little is known about the relationship between methyltransferase and cancers. Here we aimed to understand the role of methyltransferase in cancer metastasis. We found that elevated methyltransferase-like 9 (METTL9) is closely associated with the acquisition of metastatic activity in human scirrhous gastric cancers. The stable knockdown of METTL9 via an shRNA vector technique in our original metastatic cells from scirrhous gastric cancer patients significantly inhibited migration and invasion. In metastatic cells, METTL9 protein is predominantly localized in mitochondria, and the METTL9 knockdown significantly reduced mitochondrial Complex I activity. METTL9 can be a promising molecular target to inhibit peritoneal dissemination of scirrhous gastric cancers. This report is the first to describe the relationship between METTL9 and cancer metastasis.

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