RNA Sequencing of Primary Cutaneous and Breast-Implant Associated Anaplastic Large Cell Lymphomas Reveals Infrequent Fusion Transcripts and Upregulation of PI3K/AKT Signaling via Neurotrophin Pathway Genes

Cutaneous and breast implant-associated anaplastic large-cell lymphomas (cALCLs and BI-ALCLs) are two localized forms of peripheral T-cell lymphomas (PTCLs) that are recognized as distinct entities within the family of ALCL. JAK-STAT signaling is a common feature of all ALCL subtypes, whereas DUSP22/IRF4, TP63 and TYK gene rearrangements have been reported in a proportion of ALK-negative sALCLs and cALCLs. Both cALCLs and BI-ALCLs differ in their gene expression profiles compared to PTCLs; however, a direct comparison of the genomic alterations and transcriptomes of these two entities is lacking. By performing RNA sequencing of 1385 genes (TruSight RNA Pan-Cancer, Illumina) in 12 cALCLs, 10 BI-ALCLs and two anaplastic lymphoma kinase (ALK)-positive sALCLs, we identified the previously reported TYK2-NPM1 fusion in 1 cALCL (1/12, 8%), and four new intrachromosomal gene fusions in 2 BI-ALCLs (2/10, 20%) involving genes on chromosome 1 (EPS15-GNG12 and ARNT-GOLPH3L) and on chromosome 17 (MYO18A-GIT1 and NF1-GOSR1). One of the two BI-ALCL samples showed a complex karyotype, raising the possibility that genomic instability may be responsible for intra-chromosomal fusions in BI-ALCL. Moreover, transcriptional analysis revealed similar upregulation of the PI3K/Akt pathway, associated with enrichment in the expression of neurotrophin signaling genes, which was more conspicuous in BI-ALCL, as well as differences, i.e., over-expression of genes involved in the RNA polymerase II transcription program in BI-ALCL and of the RNA splicing/processing program in cALCL.

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MethCORR infers gene expression from DNA methylation and allows molecular analysis of ten common cancer types using fresh-frozen and formalin-fixed paraffin-embedded tumor samples

Clinical Epigenetics ◽

10.1186/s13148-021-01000-0 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Trine B. Mattesen ◽

Claus L. Andersen ◽

Jesper B. Bramsen

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Rna Sequencing ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Ffpe Tissue ◽

Transcriptional Analysis ◽

Sequencing Data ◽

Common Cancer ◽

Cancer Types

Abstract Background Transcriptional analysis is widely used to study the molecular biology of cancer and hold great biomarker potential for clinical patient stratification. Yet, accurate transcriptional profiling requires RNA of a high quality, which often cannot be retrieved from formalin-fixed, paraffin-embedded (FFPE) tumor tissue that is routinely collected and archived in clinical departments. To overcome this roadblock to clinical testing, we previously developed MethCORR, a method that infers gene expression from DNA methylation data, which is robustly retrieved from FFPE tissue. MethCORR was originally developed for colorectal cancer and with this study, we aim to: (1) extend the MethCORR method to 10 additional cancer types and (2) to illustrate that the inferred gene expression is accurate and clinically informative. Results Regression models to infer gene expression information from DNA methylation were developed for ten common cancer types using matched RNA sequencing and DNA methylation profiles (HumanMethylation450 BeadChip) from The Cancer Genome Atlas Project. Robust and accurate gene expression profiles were inferred for all cancer types: on average, the expression of 11,000 genes was modeled with good accuracy and an intra-sample correlation of R2 = 0.90 between inferred and measured gene expression was observed. Molecular pathway analysis and transcriptional subtyping were performed for breast, prostate, and lung cancer samples to illustrate the general usability of the inferred gene expression profiles: overall, a high correlation of r = 0.96 (Pearson) in pathway enrichment scores and a 76% correspondence in molecular subtype calls were observed when using measured and inferred gene expression as input. Finally, inferred expression from FFPE tissue correlated better with RNA sequencing data from matched fresh-frozen tissue than did RNA sequencing data from FFPE tissue (P < 0.0001; Wilcoxon rank-sum test). Conclusions In all cancers investigated, MethCORR enabled DNA methylation-based transcriptional analysis, thus enabling future analysis of cancer in situations where high-quality DNA, but not RNA, is available. Here, we provide the framework and resources for MethCORR modeling of ten common cancer types, thereby widely expanding the possibilities for transcriptional studies of archival FFPE material.

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Analyses of gene expression profiles in the rat dorsal horn of the spinal cord using RNA sequencing in chronic constriction injury rats

Journal of Neuroinflammation ◽

10.1186/s12974-018-1316-0 ◽

2018 ◽

Vol 15 (1) ◽

Cited By ~ 5

Author(s):

Hui Du ◽

Juan Shi ◽

Ming Wang ◽

Shuhong An ◽

Xingjing Guo ◽

...

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Rna Sequencing ◽

Dorsal Horn ◽

Chronic Constriction Injury ◽

Expression Profiles ◽

Gene Expression Profiles

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Transcriptomic Modification in the Cerebral Cortex following Noninvasive Brain Stimulation: RNA-Sequencing Approach

Neural Plasticity ◽

10.1155/2016/5942980 ◽

2016 ◽

Vol 2016 ◽

pp. 1-15 ◽

Cited By ~ 2

Author(s):

Ben Holmes ◽

Seung Ho Jung ◽

Jing Lu ◽

Jessica A. Wagner ◽

Liudmilla Rubbi ◽

...

Keyword(s):

Gene Expression ◽

Cerebral Cortex ◽

Rna Sequencing ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Current Intensity ◽

Beneficial Effects ◽

Group A ◽

The Impact

Transcranial direct current stimulation (tDCS) has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways), and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate) were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied.

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Two prognostically significant subtypes of high-grade lung neuroendocrine tumours independent of small-cell and large-cell neuroendocrine carcinomas identified by gene expression profiles

The Lancet ◽

10.1016/s0140-6736(04)15693-6 ◽

2004 ◽

Vol 363 (9411) ◽

pp. 775-781 ◽

Cited By ~ 183

Author(s):

Michael H Jones ◽

Carl Virtanen ◽

Daisuke Honjoh ◽

Tatsu Miyoshi ◽

Yukitoshi Satoh ◽

...

Keyword(s):

Gene Expression ◽

Neuroendocrine Tumours ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Large Cell ◽

Small Cell ◽

High Grade ◽

Neuroendocrine Carcinomas

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Breast implant – Associated Anaplastic large cell lymphoma

Hellenic Journal of Obstetrics and Gynecology ◽

10.33574/hjog.0202 ◽

2021 ◽

Vol 20 (3) ◽

pp. 117-130

Author(s):

Charilaos Ioannidis

Keyword(s):

Anaplastic Large Cell Lymphoma ◽

Soft Tissues ◽

Cell Lymphoma ◽

Breast Implant ◽

Malignant Neoplasm ◽

Large Cell ◽

Surgical Removal ◽

Treatment Change ◽

Anaplastic Lymphoma ◽

Large Cell Lymphoma

Breast Implant –Associated Anaplastic Large Cell Lymphoma is a newly recognized malignant neoplasm presenting in breasts of women who have had breast implants for cosmetic or reconstructive purposes. A review of the literature showed thatit is an uncommon, slow growing T-cell lymphoma with morphology and immunophenotype similar to anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Its clinicopathologic features and treatment, however, are unique. It usually follows an indolent clinical course, but it has the potential to form a mass, to invade locally through the periimplant breast capsule into the breast parenchyma or soft tissues and/or to spread to regional lymph nodes. Surgical removal of the implant en bloc with the whole of the capsule (explantation plus complete capsulectomy) is the treatment of choice and confers an excellent disease free and overall survival. In the few cases with metastatic disease, chemotherapy is used as an adjuvant therapy. Early detection and management convey the best prognosis; therefore clinicians, gynecologists among others, ought to be aware of this new entity and refer suspicious cases for further evaluation and treatment. Change in attitudes towards implant based surgery does not seem necessary, as long as patients are properly informed about the risk of breast implant –associated anaplastic large cell lymphoma.

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Microbial single-cell RNA sequencing by split-pool barcoding

Science ◽

10.1126/science.aba5257 ◽

2020 ◽

Vol 371 (6531) ◽

pp. eaba5257 ◽

Cited By ~ 2

Author(s):

Anna Kuchina ◽

Leandra M. Brettner ◽

Luana Paleologu ◽

Charles M. Roco ◽

Alexander B. Rosenberg ◽

...

Keyword(s):

Gene Expression ◽

Single Cell ◽

Rna Sequencing ◽

High Throughput ◽

Single Cell Analysis ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Growth Stages ◽

High Throughput Analysis ◽

Single Cell Rna Sequencing

Single-cell RNA sequencing (scRNA-seq) has become an essential tool for characterizing gene expression in eukaryotes, but current methods are incompatible with bacteria. Here, we introduce microSPLiT (microbial split-pool ligation transcriptomics), a high-throughput scRNA-seq method for Gram-negative and Gram-positive bacteria that can resolve heterogeneous transcriptional states. We applied microSPLiT to >25,000 Bacillus subtilis cells sampled at different growth stages, creating an atlas of changes in metabolism and lifestyle. We retrieved detailed gene expression profiles associated with known, but rare, states such as competence and prophage induction and also identified unexpected gene expression states, including the heterogeneous activation of a niche metabolic pathway in a subpopulation of cells. MicroSPLiT paves the way to high-throughput analysis of gene expression in bacterial communities that are otherwise not amenable to single-cell analysis, such as natural microbiota.

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A map of tumor–host interactions in glioma at single-cell resolution

GigaScience ◽

10.1093/gigascience/giaa109 ◽

2020 ◽

Vol 9 (10) ◽

Cited By ~ 3

Author(s):

Francesca Pia Caruso ◽

Luciano Garofano ◽

Fulvio D'Angelo ◽

Kai Yu ◽

Fuchou Tang ◽

...

Keyword(s):

Single Cell ◽

Rna Sequencing ◽

Cross Talk ◽

Large Scale ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Sequencing Data ◽

Host Interaction ◽

Receptor Interactions ◽

Single Cell Rna Sequencing

ABSTRACT Background Single-cell RNA sequencing is the reference technique for characterizing the heterogeneity of the tumor microenvironment. The composition of the various cell types making up the microenvironment can significantly affect the way in which the immune system activates cancer rejection mechanisms. Understanding the cross-talk signals between immune cells and cancer cells is of fundamental importance for the identification of immuno-oncology therapeutic targets. Results We present a novel method, single-cell Tumor–Host Interaction tool (scTHI), to identify significantly activated ligand–receptor interactions across clusters of cells from single-cell RNA sequencing data. We apply our approach to uncover the ligand–receptor interactions in glioma using 6 publicly available human glioma datasets encompassing 57,060 gene expression profiles from 71 patients. By leveraging this large-scale collection we show that unexpected cross-talk partners are highly conserved across different datasets in the majority of the tumor samples. This suggests that shared cross-talk mechanisms exist in glioma. Conclusions Our results provide a complete map of the active tumor–host interaction pairs in glioma that can be therapeutically exploited to reduce the immunosuppressive action of the microenvironment in brain tumor.

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The origin, fate and function of macrophages in the peripheral nervous system—an update

International Immunology ◽

10.1093/intimm/dxaa030 ◽

2020 ◽

Vol 32 (11) ◽

pp. 709-717 ◽

Cited By ~ 1

Author(s):

Lukas Amann ◽

Marco Prinz

Keyword(s):

Gene Expression ◽

Nervous System ◽

Rna Sequencing ◽

Peripheral Nervous System ◽

Expression Profiles ◽

Gene Expression Profiles ◽

New Techniques ◽

Macrophage Populations ◽

And Function ◽

First Time

Abstract The field of macrophage biology has made enormous progress over recent years. This was triggered by the advent of several new techniques such as the establishment of Cre/loxP-based transgenic mouse models that allowed for the first time delineation of the ontogeny and function of specific macrophage populations across many tissues. In addition, the introduction of new high-throughput technologies like bulk RNA sequencing and later single-cell RNA sequencing as well as advances in epigenetic analysis have helped to establish gene expression profiles, enhancer landscapes and local signaling cues that define and shape the identity of diverse macrophage populations. Nonetheless, some macrophage populations, like the ones residing in the peripheral nervous system (PNS), have not been studied in such detail yet. Here, we discuss recent studies that shed new light on the ontogeny, heterogeneity and gene expression profiles of resident macrophages in peripheral nerves and described differential activation of macrophage subsets during and after acute sciatic nerve injury.

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