Novel Fusion \u3ci\u3eKTN1-PRKD1\u3c/i\u3e in Cribriform Adenocarcinoma of Salivary Glands Located in the Parotid Gland: Case Report Including Cytologic Findings

Background Cribriform adenocarcinoma of salivary glands (CASG) is a rare, predominantly minor salivary gland tumor first described in 1999. Because the tumor shares morphologic and molecular features with polymorphous adenocarcinoma (PAC), in 2017, the World Health Organization (WHO) included CASG within the spectrum of PAC. Almost 75% of CASG harbor molecular alterations in the PRKD (Protein kinase D) gene family, and some cases show ARID1A (AT-rich interaction domain 1A)-PRKD1 or DDX3X (DEAD-Box Helicase 3 X-Linked)-PRKD1 fusions. Case presentation A 39-year-old man presented with headache and painless right cheek mass of two years duration. Imaging showed a well-circumscribed, lobulated 1.7-centimeter mass located in the superficial lobe of the right parotid gland. Fine needle aspiration (FNA) of the mass revealed a “salivary gland neoplasm of uncertain malignant potential” (SUMP). Histopathology and immunohistochemical features of the resected tumor showed a primary salivary gland neoplasm with perineural invasion suggestive of cribriform adenocarcinoma of the salivary glands (CASG). Whole exome sequencing (WES) and transcriptome sequencing (RNAseq) of the tumor revealed a novel, intrachromosomal gene fusion: KTN1 (Kinectin1)-PRKD1. Sanger sequencing and Florescent insitu hybridization (FISH) break apart probe results subsequently confirmed the presence of the fusion. The patient recovered from surgery without complications. Conclusion We report a novel fusion KTN1-PRKD1 in Cribriform Adenocarcinoma of the Salivary Glands located in the parotid gland. Importantly, this KTN1 fusion partner may account for other reports of intrachromosomal fusions in CASG in which the PRKD1 gene partner was not identified

Semiconductor microlasers with intracavity microfluidics for biomedical analyses

Recently demonstrated microfluidic chips have the potential to be useful bioanalytical tools for DNA, protein, and cellular studies. To realize this potential, means for introducing fluids, separating their components, and detection must be integrated onto the chip. The authors have investigated semiconductor laser microcavity spectroscopy as a means for ultrasensitive detection of various fluids, cells, and particulates. Two methods for implementing this laser device are illustrated. A scanning method for reading the light signals from a static fluid in the microcavity is presented. The device has a microfabricated flow structure formed between two surfaces, a vertical cavity surface-emitting laser and a glass dielectric mirror. The resonance frequencies of this Fabry-Perot microcavity are very sensitive to the dielectric properties of the fluids confined inside the cavity. Further, the resonance linewidth or cavity Q is sensitive to the optical length of the cavity, light absorption, and light scattering from the fluid and the surfaces forming the cavity. If cells or particulates are present in the fluid they confine light transverse to the cavity length and develop additional sub-frequencies between the Fabry-Perot frequencies. Thus, the spectrum of light emitted from or transmitted through the cavity comprises a wealth of information about the cavity contents

Tunable energy transfer between dipolar-coupled magnetic disks by stimulated vortex gyration

A wide variety of coupled harmonic oscillators exist in nature1. Coupling between different oscillators allows for the possibility of mutual energy transfer between them2-4 and the information-signal propagation5,6. Low-energy input signals and their transport with low-energy dissipation are the key technical factors in the design of information processing devices7. Here, utilizing the concept of coupled oscillators, we experimentally demonstrated a robust new mechanism for energy transfer between spatially separated dipolar-coupled magnetic disks - stimulated vortex gyration. Direct experimental evidence was obtained by time-resolved soft X-ray microscopy. The rate of energy transfer from one disk to the other was deduced from the two normal modes' frequency splitting caused by dipolar interaction. This mechanism provides the advantages of tunable energy transfer rate, low-power input signal, and low-energy dissipation for magnetic elements with negligible damping. Coupled vortex-state disks are promising candidates for information-signal processing devices that operate above room temperature

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum

The use of 5-methylcytosine demethylating agents in conjunction with inhibitors of histone deacetylation may offer a new therapeutic strategy for lung cancer. Monitoring the efficacy of gene demethylating treatment directly within the tumour may be difficult due to tumour location. This study determined the positive and negative predictive values of sputum and serum for detecting gene methylation in primary lung cancer. A panel of eight genes was evaluated by comparing methylation detected in the primary tumour biopsy to serum and sputum obtained from 72 patients with Stage III lung cancer. The prevalence for methylation of the eight genes in sputum (21–43%) approximated to that seen in tumours, but was 0.7–4.3-fold greater than detected in serum. Sputum was superior to serum in classifying the methylation status of genes in the tumour biopsy. The positive predictive value of the top four genes (p16, DAPK, PAX5 β, and GATA5) was 44–72% with a negative predictive value for these genes ⩾70%. The highest specificity was seen for the p16 gene, and this was associated with a odds ratio of six for methylation in the tumour when this gene was methylated in sputum. In contrast, for serum, the individual sensitivity for all genes was 6–27%. Evaluating the combined effect of methylation of at least one of the four most significant genes in sputum increased the positive predictive value to 86%. These studies demonstrate that sputum can be used effectively as a surrogate for tumour tissue to predict the methylation status of advanced lung cancer where biopsy is not feasible

Charge induced chemical dynamics in glycine probed with time resolved Auger electron spectroscopy

In the present contribution, we use x rays to monitor charge induced chemical dynamics in the photoionized amino acid glycine with femtosecond time resolution. The outgoing photoelectron leaves behind the cation in a coherent superposition of quantum mechanical eigenstates. Delayed x ray pulses track the induced coherence through resonant x ray absorption that induces Auger decay. Temporal modulation of the Auger electron signal correlated with specific ions is observed, which is governed by the initial electronic coherence and subsequent vibronic coupling to nuclear degrees of freedom. In the time resolved x ray absorption measurement, we monitor the time frequency spectra of the resulting many body quantum wave packets for a period of 175 fs along different reaction coordinates. Our experiment proves that by measuring specific fragments associated with the glycine dication as a function of the pump probe delay, one can selectively probe electronic coherences at early times associated with a few distinguishable components of the broad electronic wave packet created initially by the pump pulse in the cation. The corresponding coherent superpositions formed by subsets of electronic eigenstates and evolving along parallel dynamical pathways show different phases and time periods in the range of amp; 8722;0.3 0.1 amp; 120587; amp; 8804; amp; 120601; amp; 8804; 0.1 0.2 amp; 120587; and 18.2 1.7 amp; 8722;1.4 amp; 8804; amp; 119879; amp; 8804;23.9 1.2 amp; 8722;1.1 fs. Furthermore, for long delays, the data allow us to pinpoint the driving vibrational modes of chemical dynamics mediating charge induced bond cleavage along different reaction coordinate