FGFR1:TACC1 fusion is a frequent event in molecularly defined extraventricular neurocytoma

Members of the genus Spiroplasma are Gram-positive bacteria without cell walls. Some Spiroplasma species can cause disease in arthropods such as bees, whereas others provide their host with resistance to pathogens. Ticks also harbour Spiroplasma, but their role has not been elucidated yet. Here, the infection status and genetic diversity of Spiroplasma in ticks were investigated using samples collected from different geographic regions in Japan. A total of 712 ticks were tested for Spiroplasma infection by PCR targeting 16S rDNA, and Spiroplasma species were genetically characterized based on 16S rDNA, ITS, dnaA, and rpoB gene sequences. A total of 109 samples originating from eight tick species were positive for Spiroplasma infection, with infection rates ranging from 0% to 84% depending on the species. A linear mixed model indicated that tick species was the primary factor associated with Spiroplasma infection. Moreover, certain Spiroplasma alleles that are highly adapted to specific tick species may explain the high infection rates in Ixodes ovatus and Haemaphysalis kitaokai. A comparison of the alleles obtained suggests that horizontal transmission between tick species may not be a frequent event. These findings provide clues to understand the transmission cycle of Spiroplasma species in wild tick populations and their roles in host ticks.

Download Full-text

Integrative Genomic Analyses of Patient-Matched Intracranial and Extracranial Metastases Reveal a Novel Brain-Specific Landscape of Genetic Variants in Driver Genes of Malignant Melanoma

Cancers ◽

10.3390/cancers13040731 ◽

2021 ◽

Vol 13 (4) ◽

pp. 731

Author(s):

Renáta Váraljai ◽

Susanne Horn ◽

Antje Sucker ◽

Daniela Piercianek ◽

Verena Schmitt ◽

...

Keyword(s):

Brain Metastases ◽

Genetic Variants ◽

Genetic Alterations ◽

Metastasis Formation ◽

Driver Genes ◽

Targeted Next Generation Sequencing ◽

Paired Samples ◽

Melanoma Metastases ◽

Frequent Event ◽

Genetic Landscape

Background: Development of brain metastases in advanced melanoma patients is a frequent event that limits patients’ quality of life and survival. Despite recent insights into melanoma genetics, systematic analyses of genetic alterations in melanoma brain metastasis formation are lacking. Moreover, whether brain metastases harbor distinct genetic alterations beyond those observed at different anatomic sites of the same patient remains unknown. Experimental Design and Results: In our study, 54 intracranial and 18 corresponding extracranial melanoma metastases were analyzed for mutations using targeted next generation sequencing of 29 recurrently mutated driver genes in melanoma. In 11 of 16 paired samples, we detected nucleotide modifications in brain metastases that were absent in matched metastases at extracranial sites. Moreover, we identified novel genetic variants in ARID1A, ARID2, SMARCA4 and BAP1, genes that have not been linked to brain metastases before; albeit most frequent mutations were found in ARID1A, ARID2 and BRAF. Conclusion: Our data provide new insights into the genetic landscape of intracranial melanoma metastases supporting a branched evolution model of metastasis formation.

Download Full-text

Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia

Clinical Epigenetics ◽

10.1186/s13148-021-01013-9 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Ting-juan Zhang ◽

Zi-jun Xu ◽

Yu Gu ◽

Ji-chun Ma ◽

Xiang-mei Wen ◽

...

Keyword(s):

Dna Methylation ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Prognostic Indicator ◽

The Cancer Genome Atlas ◽

Related Gene ◽

Targeted Bisulfite Sequencing ◽

Specific Pcr ◽

Frequent Event ◽

Acute Myeloid

Abstract Background Obesity confers enhanced risk for multiple diseases including cancer. The DNA methylation alterations in obesity-related genes have been implicated in several human solid tumors. However, the underlying role and clinical implication of DNA methylation of obesity-related genes in acute myeloid leukemia (AML) has yet to be elucidated. Results In the discovery stage, we identified that DNA methylation-associated LEP expression was correlated with prognosis among obesity-related genes from the databases of The Cancer Genome Atlas. In the validation stage, we verified that LEP hypermethylation was a frequent event in AML by both targeted bisulfite sequencing and real-time quantitative methylation-specific PCR. Moreover, LEP hypermethylation, correlated with reduced LEP expression, was found to be associated with higher bone marrow blasts, lower platelets, and lower complete remission (CR) rate in AML. Importantly, survival analysis showed that LEP hypermethylation was significantly associated with shorter overall survival (OS) in AML. Moreover, multivariate analysis disclosed that LEP hypermethylation was an independent risk factor affecting CR and OS among non-M3 AML. By clinical and bioinformatics analysis, LEP may be also regulated by miR-517a/b expression in AML. Conclusions Our findings indicated that the obesity-related gene LEP methylation is associated with LEP inactivation, and acts as an independent prognostic predictor in AML.

Download Full-text

Loss of 5′-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness

Cells ◽

10.3390/cells9020492 ◽

2020 ◽

Vol 9 (2) ◽

pp. 492 ◽

Cited By ~ 1

Author(s):

Weder Pereira de Menezes ◽

Viviane Aline Oliveira Silva ◽

Izabela Natália Faria Gomes ◽

Marcela Nunes Rosa ◽

Maria Luisa Corcoll Spina ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

In Silico ◽

Glioma Cell ◽

Clinicopathological Features ◽

Migration And Invasion ◽

High Grade ◽

Methylthioadenosine Phosphorylase ◽

Frequent Event ◽

High Grade Gliomas

The 5’-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients’ clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients’ clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP’s role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas.

Download Full-text

Tight knit under stress: colony resilience to the loss of tandem leaders during relocation in an Indian ant

Royal Society Open Science ◽

10.1098/rsos.150104 ◽

2015 ◽

Vol 2 (9) ◽

pp. 150104 ◽

Cited By ~ 6

Author(s):

Swetashree Kolay ◽

Sumana Annagiri

Keyword(s):

Network Analysis ◽

Social Insects ◽

Network Structure ◽

Similar Rate ◽

Tandem Running ◽

Frequent Event ◽

Random Removal ◽

Task Organization

The movement of colonies from one nest to another is a frequent event in the lives of many social insects and is important for their survival and propagation. This goal-oriented task is accomplished by means of tandem running in some ant species, such as Diacamma indicum . Tandem leaders are central to this process as they know the location of the new nest and lead colony members to it. Relocations involving targeted removal of leaders were compared with unmanipulated and random member removal relocations. Behavioural observations were integrated with network analysis to examine the differences in the pattern of task organization at the level of individuals and that of the colony. All colonies completed relocation successfully and leaders who substituted the removed tandem leaders conducted the task at a similar rate having redistributed the task in a less skewed manner. In terms of network structure, this resilience was due to significantly higher density and outcloseness indicating increased interaction between substitute leaders. By contrast, leader–follower interactions and random removal networks showed no discernible changes. Similar explorations of other goal-oriented tasks in other societies will possibly unveil new facets in the interplay between individuals that enable the group to respond effectively to stress.

Download Full-text

High-frequency homologous recombination between duplicate chromosomal immunoglobulin mu heavy-chain constant regions

Molecular and Cellular Biology ◽

10.1128/mcb.9.12.5500-5507.1989 ◽

1989 ◽

Vol 9 (12) ◽

pp. 5500-5507

Author(s):

M D Baker

Keyword(s):

Homologous Recombination ◽

Heavy Chain ◽

High Frequency ◽

Gene Replacement ◽

Immunoglobulin M ◽

Hybridoma Cells ◽

Immunoglobulin Gene ◽

Reciprocal Recombination ◽

Base Pair Deletion ◽

Frequent Event

Homologous recombination was used in a previous study to correct a 2-base-pair deletion in the third constant domain (Cmu3) of the haploid chromosomal mu gene in a mutant hybridoma cell line by transfer of a pSV2neo vector bearing a subfragment of the normal Cmu region (M.D. Baker, N. Pennell, L. Bosnoyan, and M.J. Shulman, Proc. Natl. Acad. Sci. USA 85:6432-6436, 1988). In these experiments, both gene replacement and single reciprocal crossover events were found to restore normal, cytolytic 2,4,6-trinitrophenyl-specific immunoglobulin M production to the mutant cells. In the cases of single reciprocal recombination, the structure of the recombinant mu gene is such that the normal Cmu region, in its correct position 3' of the expressed 2,4,6-trinitrophenyl-specific heavy-chain variable region, is separated from the mutant Cmu region by the integrated vector sequences. I report here that homologous recombination occurs with high frequency between the duplicate Cmu regions in mitotically growing hybridoma cells. The homologous recombination events were easily detected since they generated hybridomas that were phenotypically different from the parental cells. Analysis of the recombinant cells suggests that gene conversion is the most frequent event, occurring between 60 and 73% of the time. The remaining events consisted of single reciprocal crossovers. Intrachromatid double reciprocal recombination was not detected. The high frequency of recombination, the ability to isolate and analyze the participants in the recombination reactions, and the capacity to generate specific modifications in the immunoglobulin Cmu regions by gene targeting suggest that this system will be useful for studying mammalian chromosomal homologous recombination. Moreover, the ability to specifically modify the chromosomal immunoglobulin genes by homologous recombination should facilitate studies of immunoglobulin gene regulation and expression and provide a more convenient of engineering specifically modified antibody.

Download Full-text

Screening for Depressive Mood During Acute Chikungunya Infection in Primary Healthcare Settings

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15112552 ◽

2018 ◽

Vol 15 (11) ◽

pp. 2552

Author(s):

Efrén Murillo-Zamora ◽

Oliver Mendoza-Cano ◽

Benjamín Trujillo-Hernández ◽

Xóchitl Trujillo ◽

Miguel Huerta ◽

...

Keyword(s):

Logistic Models ◽

Depressive Mood ◽

Self Report ◽

Chikv Infection ◽

Multicenter Cohort Study ◽

Cross Sectional ◽

Healthcare Settings ◽

Frequent Event ◽

Patient Health ◽

Sectional Analysis

Background: We aimed to screen for depressive mood experienced during acute chikungunya (CHIKV) infection, and to evaluate the association of several exposures with the risk of depressive symptoms. Methods: A cross-sectional analysis of a multicenter cohort study took place and data from 354 adult individuals with confirmed CHIKV infection were analyzed. Participants were recruited in primary health care settings and the Patient Health Questionnaire-2 (PHQ-2) was used. Prevalence odds ratios (OR) and 95% confidence intervals (CIs) estimated by means of logistic models were used. Results: Depressive mood (PHQ-2 score 3 or higher) was reported by 44.1% of individuals. Subjects with articular effusion (OR = 3.37, 95% CI 1.77–8.11), gastrointestinal manifestations (diarrhea, vomiting or abdominal pain, OR = 1.97, 95 CI 1.21–3.19), and higher length of severe arthralgia (reference ≤ 14 days: 15–30 days, OR = 3.38, 95% CI 1.78–6.41; ≥ 30 days, OR = 1.69, 95% CI 0.95–3.01) were more likely to self-report depressive mood. Increasing age (≥ 40 years old, OR = 0.55, 95% CI 0.31–0.95) and rash (OR = 0.54, 95% CI 0.30–0.98) were associated with a decreased risk of depressive mood. Conclusions: Depressive mood seemed to be a frequent event among analyzed individuals, and markers associated with its risk were identified.

Download Full-text

PTCH1 mutation is a frequent event in oesophageal basaloid squamous cell carcinoma

Mutagenesis ◽

10.1093/mutage/geu072 ◽

2014 ◽

Vol 30 (2) ◽

pp. 297-301 ◽

Cited By ~ 5

Author(s):

T. Saito ◽

H. Mitomi ◽

A. Imamhasan ◽

T. Hayashi ◽

A. Kurisaki-Arakawa ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Basaloid Squamous Cell Carcinoma ◽

Frequent Event ◽

Basaloid Squamous

Download Full-text

Atypical extraventricular neurocytoma: a rare and challenging case diagnosed on intraoperative cytology

Cytopathology ◽

10.1111/j.1365-2303.2011.00861.x ◽

2011 ◽

Vol 23 (4) ◽

pp. 270-273 ◽

Cited By ~ 9

Author(s):

N. Ghosal ◽

R. Dadlani ◽

S. Somorendra Singh ◽

A. S. Hegde

Keyword(s):

Extraventricular Neurocytoma ◽

Intraoperative Cytology

Download Full-text

RNA Recombination Plays a Major Role in Genomic Change during Circulation of Coxsackie B Viruses

Journal of Virology ◽

10.1128/jvi.78.6.2948-2955.2004 ◽

2004 ◽

Vol 78 (6) ◽

pp. 2948-2955 ◽

Cited By ~ 101

Author(s):

M. Steven Oberste ◽

Silvia Peñaranda ◽

Mark A. Pallansch

Keyword(s):

Phylogenetic Trees ◽

Clinical Isolates ◽

Human Enterovirus ◽

Rna Recombination ◽

Genomic Change ◽

Genome Region ◽

Nontranslated Region ◽

Frequent Event ◽

Coxsackie B Viruses ◽

Coxsackie B

ABSTRACT RNA recombination has been shown to occur during circulation of enteroviruses, but most studies have focused on poliovirus. To examine the role of recombination in the evolution of the coxsackie B viruses (CVB), we determined the partial sequences of four genomic intervals for multiple clinical isolates of each of the six CVB serotypes isolated from 1970 to 1996. The regions sequenced were the 5′-nontranslated region (5′-NTR) (350 nucleotides [nt]), capsid (VP4-VP2, 416 nt, and VP1, ∼320 nt), and polymerase (3D, 491 nt). Phylogenetic trees were constructed for each genome region, using the clinical isolate sequences and those of the prototype strains of all 65 enterovirus serotypes. The partial VP1 sequences of each CVB serotype were monophyletic with respect to serotype, as were the VP4-VP2 sequences, in agreement with previously published studies. In some cases, however, incongruent tree topologies suggested that intraserotypic recombination had occurred between the sequenced portions of VP2 and VP1. Outside the capsid region, however, isolates of the same serotype were not monophyletic, indicating that recombination had occurred between the 5′-NTR and capsid, the capsid and 3D, or both. Almost all clinical isolates were recombinant relative to the prototype strain of the same serotype. All of the recombination partners appear to be members of human enterovirus species B. These results suggest that recombination is a frequent event during enterovirus evolution but that there are genetic restrictions that may influence recombinational compatibility.

Download Full-text