Next-Generation Sequencing

Oncotarget

Oncotarget published this research paper on August 30, 2023 in Volume 14, entitled, “Analytic validation of NeXT Dx™, a comprehensive genomic profiling assay" by researchers from Personalis, Inc., Fremont, CA.

DOI - https://doi.org/10.18632/oncotarget.28490

Correspondence to - Richard Chen - richard.chen@Personalis.com

Abstract

We describe the analytic validation of NeXT Dx, a comprehensive genomic profiling assay to aid therapy and clinical trial selection for patients diagnosed with solid tumor cancers. Proprietary methods were utilized to perform whole exome and whole transcriptome sequencing for detection of single nucleotide variants (SNVs), insertions/deletions (indels), copy number alterations (CNAs), and gene fusions, and determination of tumor mutation burden and microsatellite instability. Variant calling is enhanced by sequencing a patient-specific normal sample from, for example, a blood specimen. This provides highly accurate somatic variant calls as well as the incidental reporting of pathogenic and likely pathogenic germline alterations. Fusion detection via RNA sequencing provides more extensive and accurate fusion calling compared to DNA-based tests. NeXT Dx features the proprietary Accuracy and Content Enhanced technology, developed to optimize sequencing and provide more uniform coverage across the exome. The exome was validated at a median sequencing depth of >500x. While variants from 401 cancer-associated genes are currently reported from the assay, the exome/transcriptome assay is broadly validated to enable reporting of additional variants as they become clinically relevant. NeXT Dx demonstrated analytic sensitivities as follows: SNVs (99.4%), indels (98.2%), CNAs (98.0%), and fusions (95.8%). The overall analytic specificity was >99.0%.

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Keywords - cancer, comprehensive genomic profiling, whole exome sequencing, whole transcriptome sequencing, tumor-normal, precision medicine

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Analytic Validation of NeXT Dx™, a Comprehensive Genomic Profiling Assay | Oncotarget

Aging (Aging-US)

Aging-US published this research paper on July 23, 2023 in Volume 15, Issue 14, entitled, “Inhibiting NLRP3 signaling in aging podocytes improves their life- and health-span" by researchers from the Division of Nephrology, University of Washington, Seattle, WA; Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH; Department of Medicine, Division of Nephrology, National University Hospital, Singapore; Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA; Department of Chemistry, University of Washington, Seattle, WA; Division of Nephrology, University of Michigan, Ann Arbor, MI; Department of Physiology and Biophysics, University of Washington, Seattle, WA; Department of Pathology, University of Chicago, Chicago, IL; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA.

DOI - https://doi.org/10.18632/aging.204897

Corresponding authors - Oliver Wessely - wesselo@ccf.org, and Stuart J. Shankland - stuartjs@uw.edu

Abstract

The decrease in the podocyte’s lifespan and health-span that typify healthy kidney aging cause a decrease in their normal structure, physiology and function. The ability to halt and even reverse these changes becomes clinically relevant when disease is superimposed on an aged kidney. RNA-sequencing of podocytes from middle-aged mice showed an inflammatory phenotype with increases in the NLRP3 inflammasome, signaling for IL2/Stat5, IL6 and TNF, interferon gamma response, allograft rejection and complement, consistent with inflammaging. Furthermore, injury-induced NLRP3 signaling in podocytes was further augmented in aged mice compared to young ones. The NLRP3 inflammasome (NLRP3, Caspase-1, IL1β IL-18) was also increased in podocytes of middle-aged humans. Higher transcript expression for NLRP3 in human glomeruli was accompanied by reduced podocyte density and increased global glomerulosclerosis and glomerular volume. Pharmacological inhibition of NLRP3 with MCC950, or gene deletion, reduced podocyte senescence and the genes typifying aging in middle-aged mice, which was accompanied by an improved podocyte lifespan and health-span. Moreover, modeling the injury-dependent increase in NLRP3 signaling in human kidney organoids confirmed the anti-senescence effect of MC9950. Finally, NLRP3 also impacted liver aging. Together, these results suggest a critical role for the NLRP3 inflammasome in podocyte and liver aging.

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Keywords - aging, kidney, podocyte, NLRP3 inflammasome, reporter

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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Inhibiting NLRP3 Signaling in Aging Podocytes Improves Their Life- and Health-Span | Aging-US

Oncotarget published this case report on July 7, 2023 in Volume 14, entitled, “Intrathoracic synovial sarcoma with BRAF V600E mutation” by researchers from the Department of Pediatric Hematology and Oncology, Gene and Cellular Therapy, Bambino Gesù Children's Hospital IRCCS, Rome, Italy; Department of Pathology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy; Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy; Department of Radiology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.

DOI - https://doi.org/10.18632/oncotarget.28475

Correspondence to - Giuseppe Maria Milano - giuseppemaria.milano@opbg.net

Abstract

We report a case of 15-year-old boy with intrathoracic synovial sarcoma who relapsed after standard chemotherapy, surgery and radiotherapy. The molecular analysis of the tumour identified a BRAF V600E mutation at time of progression of relapsed disease under third line systemic treatment. This mutation is commonly seen in melanomas and papillary thyroid cancers, but less prevalent (typically less than 5%) across a variety of other cancer types. The patient underwent selective BRAF inhibitor Vemurafenib treatment achieving partial response (PR) with a progression free survival (PFS) ratio of 1.6 months and an overall survival of 19 months, alive in continuous PR.

This case highlights the role of routinely next generation sequencing (NGS) used to drive treatment choice and to investigate extensively synovial sarcoma tumour for BRAF mutation.

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Keywords - synovial sarcoma, next-generation sequencing, BRAF V600E mutation, targeted therapy

About Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Intrathoracic Synovial Sarcoma with BRAF V600E Mutation | Oncotarget

CD Genomics

CD Genomics has extensive experience in providing support for the selection and design of microsatellite markers for a wide range of plant and animal species. Besides microsatellite genotyping, we also provide genotyping by sequencing (GBS) method, which saves time and resources.  https://www.cd-genomics.com/Microsatellite-Genotyping-Service.html

Microsatellite Genotyping Service  at CD Genomics

Oncotarget published this research paper on May 26, 2023 in Volume 14, entitled, “Association of mutation and expression of the brother of the regulator of imprinted sites (BORIS) gene with breast cancer progression" by researchers from the Department of Basic Medical Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia; Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, India; Department of Orthodontics and Dentofacial Orthopedics, ITS Dental College, Hospital and Research Centre, Greater Noida, Delhi-NCR, India; Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia; Department of Medical Laboratory, College of Applied Medical Sciences, Qassim University, Qassim, Saudi Arabia; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Surgical Oncology, BRA- IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India; Department of Neurology, Henry Ford Health System, Detroit, MI; School of Biotechnology, Jawahar Lal Nehru University, New Delhi, India.

DOI - https://doi.org/10.18632/oncotarget.28442

Correspondence to - Mohammad Salman Akhtar - mdsalmanakhtar@yahoo.com, milyas@bu.edu.sa

Abstract

Introduction: The BORIS, 11 zinc-finger transcription factors, is a member of the cancer-testis antigen (CTA) family. It is mapped to chromosome number 20q13.2 and this region is genetically linked to the early onset of breast cancer. The current study analyzed the correlation between BORIS mutations and the expression of the protein in breast cancer cases.

Materials and Methods: A population-based study including a total of 155 breast cancer tissue samples and an equal number of normal adjacent tissues from Indian female breast cancer patients was carried out. Mutations of the BORIS gene were detected by polymerase chain reaction-single standard confirmation polymorphisms (PCR-SSCP) and automated DNA sequencing and by immunohistochemistry for BORIS protein expression were performed. The observed findings were correlated with several clinicopathological parameters to find out the clinical relevance of associations.

Results: Of all the cases 16.12% (25/155) showed mutations in the BORIS gene. The observed mutations present on codon 329 are missense, leading to Val> Ile (G>A) change on exon 5 of the BORIS gene. A significant association was observed between mutations of the BORIS gene and some clinicopathological features like nodal status (p = 0.013), estrogen receptor (ER) expression (p = 0.008), progesterone receptor (PR) expression (p = 0.039), clinical stage (p = 0.010) and menopausal status (p = 0.023). The protein expression analysis showed 20.64% (32/155) samples showing low or no expression (+), 34.19% (53/155) with moderate expression (++), and 45.17% (70/155) showing high expression (+++) of BORIS protein. A significant association was observed between the expression of BORIS protein and clinicopathological features like clinical stage (p = 0.013), nodal status (p = 0.049), ER expression (p = 0.039), and PR expression (p = 0.027). When mutation and protein expression were correlated in combination with clinicopathological parameters a significant association was observed in the category of high (+++) level of BORIS protein expression (p = 0.017).

Conclusion: The BORIS mutations and high protein expression occur frequently in carcinoma of the breast suggesting their association with the onset and progression of breast carcinoma. Further, the BORIS has the potential to be used as a biomarker.

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Keywords - BORIS, breast cancer, mutation, transcription factor, PCR-SSCP

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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BORIS Gene Mutation and Expression: Link to Breast Cancer Progression

To support the increasing research interest in small RNA, CD Genomics is offering the qualified small RNA sequencing service that covers novel small RNA discovery, mutation characterization, and expression profiling of small RNAs by leveraging of advanced NGS technologies and data analysis pipeline.	https://www.cd-genomics.com/Small-RNA.html

Small RNA Sequencing: Challengs and Workflow

CD Genomics has been providing the accurate and affordable whole genome sequencing service for couple of years. We combine both Illumina (short reads) and PacBio (long reads) platforms to achieve whole genome de novo assemblies and re-sequencing for viruses, microbes, plants, animals and humans.	https://www.cd-genomics.com/Whole-Genome-Sequencing.html

Methods and Workflow of Whole Genome Sequencing

Teach Me in 10

In this Teach me in 10, Senior Field Application Scientist Nick Hapshe explains: (1) What NGS adapters are, and how they are used in library construction; (2) what sequencing indexes are, and why they are important; (3) How different types of adapters and indexing strategies can improve the quality of NGS data while reducing sequencing costs; and (4) What unique molecular identifiers (UMIs) are, and how they can increase accuracy in NGS data.

An Overview of NGS Adapters for Ligation-based Library Preparation

RNA-Seq is the premier tool for mapping and quantifying transcriptomes by utilizing next-generation sequencing (NGS) technology. The transcriptome refers to the complete set of transcripts in a cell, which provides information on the transcript level for a specific developmental stage or physiological condition. Understanding the transcriptome is necessary for interpreting the functional elements of the genome and understanding development and disease. The key purpose of transcriptomics includes cataloging all species of transcripts; determining the transcriptional structure of genes; and quantifying the expression levels of each transcript under different conditions.

The Development and Workflow of RNA-seq, Learn more at https://www.cd-genomics.com/resourse-Bioinformatics-Workflow-of-RNA-Seq.html

Next-Generation Sequencing

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