Mutation and Transcriptional Profiling of Formalin-Fixed Paraffin Embedded Specimens as Companion Methods to Immunohistochemistry for Determining Therapeutic Targets in Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Pilot of Proof of Principle
Nabil F. Saba,Malania M. Wilson,Gregory H. Doho,Juliana DaSilva,R. Benjamin Isett,Scott Newman,Zhuo Georgia Chen,Kelly R. Magliocca,Michael R. Rossi +8 more
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TLDR
These preliminary experiments are among the earliest to combine both mutational and gene expression profiles using Ion Torrent and NanoString technologies and show the utility of these methods with routine FFPE clinical specimens to identify potential therapeutic targets which could be readily applied in a clinical trial setting.Abstract:
The role of molecular methods in the diagnosis of head and neck cancer is rapidly evolving and holds great potential for improving outcomes for all patients who suffer from this diverse group of malignancies . However, there is considerable debate as to the best clinical approaches, particularly for Next Generation Sequencing (NGS). The choices of NGS methods such as whole exome, whole genome, whole transcriptomes (RNA-Seq) or multiple gene resequencing panels, each have strengths and weakness based on data quality, the size of the data, the turnaround time for data analysis, and clinical actionability. There have also been a variety of gene expression signatures established from microarray studies that correlate with relapse and response to treatment, but none of these methods have been implemented as standard of care for oropharyngeal squamous cell carcinoma (OPSCC). Because many genomic methodologies are still far from the capabilities of most clinical laboratories, we chose to explore the use of a combination of off the shelf targeted mutation analysis and gene expression analysis methods to complement standard anatomical pathology methods. Specifically, we have used the Ion Torrent AmpliSeq cancer panel in combination with the NanoString nCounter Human Cancer Reference Kit on 8 formalin-fixed paraffin embedded (FFPE) OPSCC tumor specimens, (4) HPV-positive and (4) HPV-negative. Differential expression analysis between HPV-positive and negative groups showed that expression of several genes was highly likely to correlate with HPV status. For example, WNT1, PDGFA and OGG1 were all over-expressed in the positive group. Our results show the utility of these methods with routine FFPE clinical specimens to identify potential therapeutic targets which could be readily applied in a clinical trial setting for clinical laboratories lacking the instrumentation or bioinformatics infrastructure to support comprehensive genomics workflows. To the best of our knowledge, these preliminary experiments are among the earliest to combine both mutational and gene expression profiles using Ion Torrent and NanoString technologies. This reports serves as a proof of principle methodology in OPSCC.read more
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Journal ArticleDOI
Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification.
Rick Kamps,Rita D. Brandão,Bianca J.C. van den Bosch,Aimee D C Paulussen,Sofia Xanthoulea,Marinus J. Blok,Andrea Romano +6 more
TL;DR: This review describes the recent technological developments in NGS applied to the field of oncology and a number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA- sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequenced to identify risk modifiers and application for pre-implantation genetic diagnosis, cancer somatic mutation analysis, pharmacogenetics and liquid biopsy.
Journal Article
The Mutational Landscape of Head and Neck Squamous Cell Carcinoma
Nicolas Stransky,Ann Marie Egloff,Aaron D. Tward,Aleksandar Kostic,Kristian Cibulskis,Andrey Sivachenko,Gregory Kryukov,Michael S. Lawrence,Carrie Sougnez,Aaron McKenna,Erica Shefler,Alex H. Ramos,Petar Stojanov,Scott L. Carter,Douglas Voet,Maria L. Cortes,Daniel Auclair,Michael F. Berger,Gordon Saksena,Candace Guiducci,Robert C. Onofrio,Melissa Parkin,Marjorie Romkes,Joel L. Weissfeld,Raja R. Seethala,Lin Wang,Claudia Rangel-Escareño,Juan Carlos Fernández-López,Alfredo Hidalgo-Miranda,Jorge Melendez-Zajgla,Wendy Winckler,Kristin Ardlie,Stacey Gabriel,Matthew Meyerson,Eric S. Lander,Gad Getz,Todd R. Golub,Levi A. Garraway,Jennifer R. Grandis +38 more
TL;DR: The results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms and suggest the development of targeted therapies for head and neck cancer may be hindered by complex mutational profiles.
Journal ArticleDOI
Evaluating Robustness and Sensitivity of the NanoString Technologies nCounter Platform to Enable Multiplexed Gene Expression Analysis of Clinical Samples
Margaret Veldman-Jones,Roz Brant,Claire Rooney,Catherine Geh,Hollie Emery,Chris Harbron,Mark Wappett,Alan Sharpe,Michael Dymond,J. Carl Barrett,Elizabeth A. Harrington,Gayle Marshall +11 more
TL;DR: This study demonstrates that Nanostring offers several key advantages, including sensitivity, reproducibility, technical robustness, and utility for clinical application, as well as evaluating the NanoString Technologies nCounter platform.
Journal ArticleDOI
Genomic Landscape of Human Papillomavirus–Associated Cancers
TL;DR: A number of the alterations identified are potentially targetable, which may lead to advances in the treatment of HPV-associated cancers and potential therapeutic opportunities for HPV-driven malignancies.
Journal ArticleDOI
Cell-of-origin of diffuse large B-cell lymphomas determined by the Lymph2Cx assay: better prognostic indicator than Hans algorithm.
TL;DR: The Lymph2Cx assay is a robust, reliable method for predicting the outcome of patients withDLBCL treated with R-CHOP chemotherapy, and no significant differences were observed in survival between the two patient subgroups with DLBCL types classified by the Hans algorithm.
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