Using genetic signatures to better classify spinal neurons

Liposarcoma (LPS) is an adult soft tissue malignancy that arises from fat tissue, where well-differentiated (WD) and dedifferentiated (DD) forms are the most common. DDLPS represents the progression of WDLPS into a more aggressive high-grade and metastatic form. Although a few DNA copy-number amplifications are known to be specifically found in WD- or DDLPS, systematic genetic differences that signify subtype determination between WDLPS and DDLPS remain unclear. Here, we profiled the genome and transcriptome of 38 LPS tumors to uncover the genetic signatures of subtype differences. Replication-dependent histone (RD-HIST) mRNAs were highly elevated and their regulation was disrupted in a subset of DDLPS, increasing cellular histone molecule levels, as measured using RNA-seq (the averaged fold change of 53 RD-HIST genes between the DD and WD samples was 10.9) and immunohistochemistry. The change was not observed in normal tissues. Integrated whole-exome sequencing, RNA-seq, and methylation analyses revealed that the overexpressed HMGA2 (the fold change between DD and WD samples was 7.3) was responsible for the increased RD-HIST level, leading to aberrant cell proliferation. Therefore, HMGA2-mediated elevation of RD-HISTs were crucial events in determining the aggressiveness of DDLPS, which may serve as a biomarker for prognosis prediction for liposarcoma patients.

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Distinctive genetic signatures of two fairy shrimp species with overlapping ranges in Iberian temporary ponds

Freshwater Biology ◽

10.1111/fwb.13782 ◽

2021 ◽

Author(s):

Regina Lopes da Cunha ◽

Jordi Sala ◽

Margarida Machado ◽

Dani Boix ◽

Celine Madeira ◽

...

Keyword(s):

Temporary Ponds ◽

Fairy Shrimp ◽

Shrimp Species ◽

Genetic Signatures

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SP-0017: Development and validation of genetic signatures in radiation oncology

Radiotherapy and Oncology ◽

10.1016/s0167-8140(21)00043-8 ◽

2020 ◽

Vol 152 ◽

pp. S4

Author(s):

C. West

Keyword(s):

Radiation Oncology ◽

Genetic Signatures ◽

Development And Validation

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Developmental-Dependent Action of Microtubule Depolymerization on the Function and Structure of Synaptic Glycine Receptor Clusters in Spinal Neurons

Journal of Neurophysiology ◽

10.1152/jn.00364.2003 ◽

2004 ◽

Vol 91 (2) ◽

pp. 1036-1049 ◽

Cited By ~ 27

Author(s):

Brigitte van Zundert ◽

Francisco J. Alvarez ◽

Juan Carlos Tapia ◽

Hermes H. Yeh ◽

Emilio Diaz ◽

...

Keyword(s):

Average Length ◽

Glycine Receptor ◽

Colchicine Treatment ◽

Morphological Properties ◽

Microtubule Depolymerization ◽

Spinal Neurons ◽

Functional Changes ◽

Microtubule Disruption ◽

Immature Neurons ◽

Mature Neurons

Microtubules have been proposed to interact with gephyrin/glycine receptors (GlyRs) in synaptic aggregates. However, the consequence of microtubule disruption on the structure of postsynaptic GlyR/gephyrin clusters is controversial and possible alterations in function are largely unknown. In this study, we have examined the physiological and morphological properties of GlyR/gephyrin clusters after colchicine treatment in cultured spinal neurons during development. In immature neurons (5-7 DIV), disruption of microtubules resulted in a 33 ± 4% decrease in the peak amplitude and a 72 ± 15% reduction in the frequency of spontaneous glycinergic miniature postsynaptic currents (mIPSCs) recorded in whole cell mode. However, similar colchicine treatments resulted in smaller effects on 10-12 DIV neurons and no effect on mature neurons (15-17 DIV). The decrease in glycinergic mIPSC amplitude and frequency reflects postsynaptic actions of colchicine, since postsynaptic stabilization of microtubules with GTP prevented both actions and similar reductions in mIPSC frequency were obtained by modifying the Cl- driving force to obtain parallel reductions in mIPSC amplitude. Confocal microscopy revealed that colchicine reduced the average length and immunofluorescence intensity of synaptic gephyrin/GlyR clusters in immature (approximately 30%) and intermediate (approximately 15%) neurons, but not in mature clusters. Thus the structural and functional changes of postsynaptic gephyrin/GlyR clusters after colchicine treatment were tightly correlated. Finally, RT-PCR, kinetic analysis and picrotoxin blockade of glycinergic mIPSCs indicated a reorganization of the postsynaptic region from containing both α2β and α1β GlyRs in immature neurons to only α1β GlyRs in mature neurons. Microtubule disruption preferentially affected postsynaptic sites containing α2β-containing synaptic receptors.

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Pharmacogenomic Biomarkers in Docetaxel Treatment of Prostate Cancer: From Discovery to Implementation

Genes ◽

10.3390/genes10080599 ◽

2019 ◽

Vol 10 (8) ◽

pp. 599 ◽

Cited By ~ 1

Author(s):

Reka Varnai ◽

Leena M. Koskinen ◽

Laura E. Mäntylä ◽

Istvan Szabo ◽

Liesel M. FitzGerald ◽

...

Keyword(s):

Prostate Cancer ◽

Treatment Guidelines ◽

Individual Variability ◽

Castration Resistant Prostate Cancer ◽

Predictive Capacity ◽

Current State ◽

Docetaxel Treatment ◽

High Heritability ◽

Treatment Procedures ◽

Genetic Signatures

Prostate cancer is the fifth leading cause of male cancer death worldwide. Although docetaxel chemotherapy has been used for more than fifteen years to treat metastatic castration resistant prostate cancer, the high inter-individual variability of treatment efficacy and toxicity is still not well understood. Since prostate cancer has a high heritability, inherited biomarkers of the genomic signature may be appropriate tools to guide treatment. In this review, we provide an extensive overview and discuss the current state of the art of pharmacogenomic biomarkers modulating docetaxel treatment of prostate cancer. This includes (1) research studies with a focus on germline genomic biomarkers, (2) clinical trials including a range of genetic signatures, and (3) their implementation in treatment guidelines. Based on this work, we suggest that one of the most promising approaches to improve clinical predictive capacity of pharmacogenomic biomarkers in docetaxel treatment of prostate cancer is the use of compound, multigene pharmacogenomic panels defined by specific clinical outcome measures. In conclusion, we discuss the challenges of integrating prostate cancer pharmacogenomic biomarkers into the clinic and the strategies that can be employed to allow a more comprehensive, evidence-based approach to facilitate their clinical integration. Expanding the integration of pharmacogenetic markers in prostate cancer treatment procedures will enhance precision medicine and ultimately improve patient outcomes.

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