Next-generation sequencing (NGS) has transformed the field of oncology. Early successes in identifying and targeting oncogenic drivers of solid tumors have set the foundation for genomics guided precision medicine; but, for hematological malignancies, the path to precision medicine is a lot more complex.
Within the hematologic oncology space, there is a spectrum of biologically related, but clinically heterogeneous diseases. In part, the differences between patients are driven by the particular combination of genetic mutations each disease acquires during its evolution. To effectively treat and manage myeloid malignancies, hematologist oncologists need highly parallel, highly sensitive assays that (1) enable the simultaneous analysis of multiple genes and (2) are coupled with indication-specific bioinformatic pipelines that provide information on disease classification, prognostication, treatment selection, and monitoring.
In this application note, we discuss the importance of streamlined clinical NGS workflows within the hematologic-oncology space. Learn how to develop a robust, automated, and streamlined NGS analysis pipeline for the interpretation and reporting of genomic alterations associated with hematological malignancies.
Read and download the application note >
On April 22, Nature Medicine published the first results from the UK's TARGET (Tumor chARacterisation to Guide Experimental Targeted therapy) study. The letter, written by researchers funded by Cancer Research UK, The Christie Charity, AstraZeneca, and the NIHR Manchester Biomedical Research Centre (BRC), adds new evidence for the feasibility and potential utility of liquid biopsy to identify clinically actionable mutations and guide clinical trial enrollment for patients with advanced cancer.
Currently, enrollment to trials depends on a patient's type of cancer or genetic data obtained from an invasive tumor biopsy, which is often months or years old and may not represent a patient's current disease due to the tumor's evolutionary changes.
TARGET is a molecular profiling program with the primary aim to match patients with different types of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations across a 641 cancer-associated-gene panel in a single ctDNA assay. In the first of the two-part trial, the investigators were able to collect, process and analyze blood samples from 100 patients in the Manchester area.
The results show that a small volume of blood can contain up-to-date genetic information about a patient's cancer to inform treatment choices. In this feasibility study of the first 100 patients, 11 were molecularly matched and enrolled into an available therapy.
Investigators used QIAGEN Clinical Insight (QCI) to identify the clinically actionable variants and geographically available clinical trials, stating:
Functional annotation of somatic variants was performed using ANNOVAR, the resultant VCF file was analyzed through the QIAGEN Clinical Insight for Somatic Cancer platform and reports were generated for discussion in the TARGET Molecular Tumor Board. ‘Actionable’ was defined as a target of known pathogenic significance for which either a licensed or experimental agent or relevant clinical trial was available at the time of discussion.
The investigators go on to describe the importance of using clinical interpretation and reporting tools that are connected to comprehensive knowledge resources needed to minimize the number of variants of unknown significance (VUS) with evidence. As they explain, it is nearly impossible for tumor boards to have knowledge of every actionable variant:
A potential reason why large molecular screening programs have traditionally allocated only 10–15% of patients to studies may be in the interpretation of variants of unknown significance7,8,9. It is challenging for any MTB to have knowledge of all possible variants, and databases are in development for pooling relevance of variants of unknown significance23,24. We addressed this issue by accessing software packages to aid interpretation of the relevance of specific variants and to identify appropriate trials in different regions of the United Kingdom or Europe. The QIAGEN Clinical Interface software package was considered valuable in differentiating actionable mutations (and recommended matched therapies) from those of unlikely clinical relevance, and provided tiering following ACMG/AMP/CAP guidelines.
The researchers now hope the second part of TARGET, which is already underway, will show how often the blood test is successful at matching patients to early phase clinical trials and the impact this has on their overall survival. There is also an option of referring patients to other clinical trial sites, if suitable matched trials are available in other parts of the country--another great feature of QCI.
Reference: *Rothwell, et al. Utility of ctDNA to support patient selection for early phase clinical trials: The TARGET Study. Nature Medicine. (2019) DOI: https://doi.org/10.1038/s41591-019-0380-z
This year ESHG is celebrating it's 50th anniversary in beautiful Copenhagen! Come and meet us at booths 540 and 542 and find out how our solutions are helping to unlock the complexities of liquid biopsy, clinical oncology, hereditary disease, microbial genomics and more.
We're also hosting a lunchtime Corporate Satellite Meeting on Sunday, May 28 where lunch boxes are provided. Here's the schedule:
Using seamlessly integrated preanalytical, next-generation sequencing and bioinformatics solutions, and leveraging expertise in translational and clinical research to refine our understanding of human genetics and diseases
Time: 11.15 a.m. – 12.50 p.m.
Room: Berlin
Chair: Anja Wild and Phoebe Loh, QIAGEN, Hilden
11.15 a.m. – 11.20 a.m.
Welcome
11.20 a.m. – 11.50 a.m.
Molecular analysis of thyroid nodules – detection of gene mutations and fusion genes by DNA/RNA sequencing
Dr. Egbert Schulze, Molecular Genetics Laboratory, Heidelberg, Germany
11.50 a.m. – 12.15 p.m.
Circulating Cell Free DNA Pre-Analytics: Importance of ccfDNA Stabilization and Extraction for Liquid Biopsy Applications
Dr. Dominic O’Neil, QIAGEN, Hilden, Germany
12.15 p.m. – 12.45 p.m.
Leveraging Unique Molecular Indices to improve low-frequency variant estimation and calling in QIASeq v3 panels
Bjarni Vilhjalmsson, QIAGEN, Aarhus, Denmark
12.45 p.m. – 12.50 p.m.
Closing
As usual, we've prepared some poster presentations covering the latest enhancements to various application areas:
Electronic-poster number: E-P16.13
Presenter: Stuart Tugendreich, Principal Scientist, QIAGEN Bioinformatics
Title: Integrative approach to biomarker discovery by performing comparative analysis of two cancers Hepatocellular carcinoma and Endometrioid endometrial carcinoma using genetics and transcriptomics from RNA sequencing data.
Poster number: P14.049A
When: 10.15 a.m. - 11.15 a.m., Sunday, May 28
Presenter: Rupert Yip, Director of Global Product Management, Genetic Disease, QIAGEN Bioinformatics
Title: Prioritizing causal variants for rare, inherited syndromes, using patient phenotypes
We look forward to seeing as many of you there as possible.
Vi ses!
ASHG 2016 was an exciting event for us. We loved the beautiful city of Vancouver, BC, and our calendars were packed with speakerships, poster presentations and meetings with peers and colleagues. We also announced our new Sample-to-Insight solutions for liquid biopsies and hereditary diseases — which included our bioinformatics solutions, and our booth was buzzing with people who wanted to learn more. Our public-facing ASHG activities were a germane reflection of the event’s overarching theme: “Sharing Discoveries. Shaping our Future.” Over the course of five days during ASHG, QIAGEN Bioinformatics staff delivered six separate in-booth presentations, five poster presentations and an educational workshop focused on liquid biopsy, RNA-seq, and hereditary diseases.
If you missed them, or would like to see them again, you can see Jean-Noel Billaud's presentation on an Integrative approach to biomarker discovery: Comparative analysis of two cancers using genomics and transcriptomics from RNA sequencing data here, and Helge Martens' on Rapid identification and prioritization of pathogenic variants associated with anomalies of the kidneys and urinary tract here.
We were not the only ones who were busy during ASHG. The Broad Institute’s new beta of its Genome Aggregation Database, or “gnomAD” was announced, which boasts information from 126,216 human exomes and 15,136 whole human genomes and doubles the number of exomes available from the ExAC population database. This news resonated strongly with us because we’re championing similar efforts with the Allele Frequency Community — our opt-in community resource which encourages the sharing of anonymized, pooled frequency statistics among laboratories. The industry’s continued drumbeat toward precision medicine was another recurring theme, going hand-in-hand with the strong focus on Canada’s efforts to adopt its own version of 2008’s U.S. Genetic Information Nondiscrimination Act. We also saw continued buzz around CRISPR technology, with several ASHG sessions dedicated to both the implications and obligations inherent in genome editing technology.
We hope you enjoyed your time at ASHG and we hope to see you soon. If you have questions about liquid biopsy or related solutions, do not hesitate to contact us.
Our next big event will be AMP 2016 in Charlotte, NC from Nov. 10-12 and the NGS Congress in London from Nov. 10-11. Keep an eye on this site for updates about what we’ll be doing there. We hope you enjoyed your time at ASHG and we hope to see you soon. If you have questions about liquid biopsy or related solutions, do not hesitate to contact us.
Part four of our webinar series on liquid biopsies:
Circulating cell-free DNA purification, sequencing and data interpretation
Identification and monitoring of cancer mutations of circulating cell-free DNA (cfDNA) is a key application in liquid biopsy. In the webinar series, we discuss various new technologies and present a complete sample to insight workflow for cfDNA mutation analysis. In this webinar, we show how mutations can be best identified from this type of data and how they can be interpreted. Anika Joecker, Global Solution Product Manager Bioinformatics, Clinical Program, present our solutions for analysis and interpretation of cell free DNA.
https://clcbio.23video.com/v.ihtml/player.html?token=1d44ef16da780f0a29b214aad388d7cd&source=embed&photo%5fid=13428465New, powerful bioinformatics tool: The RNA-Seq Explorer Solution
Today we announced our new RNA-Seq Explorer Solution — a powerful bioinformatics tool that combines Ingenuity® Pathway Analysis™ and Biomedical Genomics Workbench® to generate clear insights for research into improved cancer detection, diagnosis, and treatment. One of the most compelling benefits of the RNA-Seq Explorer Solution is that it allows you to focus on biology, giving you the tools to drive your research forward and to publish novel findings. It transforms raw data from liquid biopsies — one of the most promising new ways to detect and characterize cancer — into clear, accurate, actionable insights. Ultimately, we believe that a powerful bioinformatics-driven liquid biopsy solution like this one will vastly improve precision medicine and cancer management.
Principal Scientist Jean-Noel Billaud is presenting data from this new solution at AACR at our theater presentation on Tuesday, April 19, at 3:00 p.m. We hope you’ll come by to hear the finer points of our new RNA-Seq Explorer Solution. You’re of course also welcome to stop by our booth #741 for at chat.
Get the full overview of our activites at AACR.
For more details on the RNA-Seq Explorer Solution, please read the official press release below.
Press release
QIAGEN launches streamlined bioinformatics for RNA sequencing of liquid biopsies
RNA-seq Explorer Solution generates clear insights for cancer ‘omics’ analyses
Hilden, Germany, and Germantown, Maryland, April 14, 2016 – QIAGEN N.V. (NASDAQ: QGEN; Frankfurt Prime Standard: QIA) today announced introduction of its unique RNA-seq Explorer Solution, a bioinformatics-driven approach to analysis and interpretation of “omics” data from liquid biopsy-based research. RNA-seq Explorer Solution is a new tool which integrates Ingenuity® Pathway Analysis™ Biomedical Genomics Workbench® and other QIAGEN bioinformatics solutions to generate clear insights for research into improved detection, diagnosis and treatment of cancer. The solution will be demonstrated at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans.
“The RNA-seq Explorer Solution provides the most powerful bioinformatics tool for the analysis and interpretation of RNA sequencing data from liquid biopsies, including from tumor-derived exosomes. Next-generation sequencing of liquid biopsies, one of the most promising new ways of detecting and characterizing cancer, demands the highest-accuracy tools to make sense of inherently noisy data,” said Dr. Laura Furmanski, Senior Vice President and head of QIAGEN’s Bioinformatics Business Area. “QIAGEN’s streamlined RNA solution transforms raw data from liquid biopsies into valuable insights – a significant milestone for liquid biopsy analysis of indications such as cancer. The best bioinformatics will drive progress in precision medicine and cancer management.”
Liquid biopsy is a non-invasive method using samples of body fluids such as blood to detect and profile diseases such as cancer at the earliest stage, resulting in more successful prognosis and treatment. One liquid biopsy approach extracts DNA or RNA from tumor-derived exosomes, tiny enclosures that circulate in body fluids. In an RNA-seq workflow, scientists analyze and interpret exosomal RNA to determine gene expression profiles, identifying regulatory networks and potential isoforms of biological significance.
RNA-seq Explorer Solution facilitates simple, accurate discovery and validation of biomarkers, enabling researchers to go from raw data in FASTQ format to significant insights that home in on the genetic drivers of cancer. The solution draws upon QIAGEN’s Ingenuity Pathway Analysis (IPA), an all-in-one, web-based software application that enables analysis, integration and understanding of expression data. IPA is backed by the expert-curated Ingenuity Knowledge Base of highly structured, detail-rich biological and chemical findings. RNA-seq Explorer Solution also integrates QIAGEN’s Biomedical Genomics Workbench, a comprehensive data analysis platform that offers end-to-end workflows and tools for the alignment, normalization and statistical analysis of NGS experimental results.
In addition to demonstrating of the new RNA-seq solution at its booth at the AACR meeting, QIAGEN Bioinformatics recently released a four-part webinar series; the company will also have a sustained presence at the event. Click here for more details.
Leadership in liquid biopsies
RNA-seq Explorer Solution complements QIAGEN’s industry-leading liquid biopsy portfolio, which is spanning sample technologies, assay technologies and bioinformatics. It includes gold-standard solutions for the extraction of cell-free, circulating nucleic acids (cfDNA), circulating tumor cells (CTCs), and exosomes. In partnership with pharmaceutical companies, QIAGEN is developing and commercializing the broadest portfolio of companion diagnostics based on liquid biopsies, including the therascreen EGFR RGQ Plasma PCR kit, the first ever CE-IVD-marked blood-based test to guide treatment decisions for solid tumors.
About QIAGEN
QIAGEN N.V., a Netherlands-based holding company, is the leading global provider of Sample to Insight solutions to transform biological materials into valuable molecular insights. QIAGEN sample technologies isolate and process DNA, RNA and proteins from blood, tissue and other materials. Assay technologies make these biomolecules visible and ready for analysis. Bioinformatics software and knowledge bases interpret data to report relevant, actionable insights. Automation solutions tie these together in seamless and cost-effective molecular testing workflows. QIAGEN provides these workflows to more than 500,000 customers around the world in Molecular Diagnostics (human healthcare), Applied Testing (forensics, veterinary testing and food safety), Pharma (pharmaceutical and biotechnology companies) and Academia (life sciences research). As of September 30, 2015, QIAGEN employed approximately 4,600 people in over 35 locations worldwide. Further information can be found at http://www.qiagen.com.
Certain of the statements contained in this news release may be considered forward-looking statements within the meaning of Section 27A of the U.S. Securities Act of 1933, as amended, and Section 21E of the U.S. Securities Exchange Act of 1934, as amended. To the extent that any of the statements contained herein relating to QIAGEN's products, markets, strategy or operating results, including without limitation its expected operating results, are forward-looking, such statements are based on current expectations and assumptions that involve a number of uncertainties and risks. Such uncertainties and risks include, but are not limited to, risks associated with management of growth and international operations (including the effects of currency fluctuations, regulatory processes and dependence on logistics), variability of operating results and allocations between customer classes, the commercial development of markets for our products in applied testing, personalized healthcare, clinical research, proteomics, women's health/HPV testing and nucleic acid-based molecular diagnostics; changing relationships with customers, suppliers and strategic partners; competition; rapid or unexpected changes in technologies; fluctuations in demand for QIAGEN's products (including fluctuations due to general economic conditions, the level and timing of customers' funding, budgets and other factors); our ability to obtain regulatory approval of our products; difficulties in successfully adapting QIAGEN's products to integrated solutions and producing such products; the ability of QIAGEN to identify and develop new products and to differentiate and protect our products from competitors' products; market acceptance of QIAGEN's new products, the consummation of acquisitions, and the integration of acquired technologies and businesses. For further information, please refer to the discussions in reports that QIAGEN has filed with, or furnished to, the U.S. Securities and Exchange Commission (SEC).
Liquid biopsies show promise for cancer research, but technical challenges remain
Preparing for this year’s annual meeting of the American Association for Cancer Research (AACR), we’ve been thinking about some of the most promising recent technology trends in oncology. One of our favorites is the advances in liquid biopsies as a way to earlier monitor cancer progression, and get a better sense of the genetic variation or expression profile present in a primary tumor or metastatic sites.
Most liquid biopsy studies look for one of three materials: cell-free DNA (cfDNA), circulating tumor cells (CTCs), or exosomes. As its name suggests, cfDNA is the genetic material released into the bloodstream from tumor cells that get lysed during apoptosis or some other process. CTCs are intact cells; in addition to the genetic information they can reveal about a tumor, they’re appealing because they may be cultured for a more sophisticated, longer-term analysis of how these cells function. Exosomes are vesicles released by cells as part of a cell-to-cell signaling network, among other important functions. They may contain RNAs or proteins produced by tumors or other cancerous cells. As scientists make inroads in liquid biopsy studies, it is becoming clear that a comprehensive picture of cancer requires information from as many of these sources as possible.
The biggest challenges with liquid biopsies right now involve finding signal in the noise. This occurs in two different phases: first, when blood or plasma is originally drawn from a patient. The cfDNA, CTCs, and exosomes from cancer cells are wildly outnumbered by material from healthy cells. Typically, liquid biopsies yield vanishingly small samples of interest for cancer research; significant efforts are underway to help solve this problem. A related challenge takes place in data analysis, where again the signal, identifying the driver variant or elucidating mechanisms driving the expression profile, from DNA or cells originating from a tumor can be very difficult to find in the wild-type noise. Analysis and interpretation solutions are being used to overcome this challenge as well.
We believe that liquid biopsies have the potential to transform the diagnosis and treatment of cancer patients. We’re delivering solutions that can help scientists conduct, analyse, and interpret liquid biopsy studies with greater precision and reliability.
We look forward to hearing more about this topic at AACR.
For additional updates, please visit the Biomarker Insights blog or see the schedule for our activities at AACR.
Webinar series on liquid biopsy
Circulating cell-free DNA purification, sequencing and data interpretation
Identification and monitoring of cancer mutations of circulating cell-free DNA (cfDNA) is a key application in liquid biopsy. In this webinar series, we will discuss various new technologies and present a complete sample to insight workflow for cfDNA mutation analysis.
The themes of the four webinars will be:
• Part 1: New technology and workflow for integrated collection, stabilization and purification of circulating cell-free DNA
• Part 2: Overcome challenges of cfDNA with automated and standardized extraction processes
• Part 3: Next generation sequencing technology for cfDNA analysis
• Part 4: Analysis and interpretation of cell free DNA (cfDNA)
In part 4, Anika Joecker, Global Solution Product Manager Bioinformatics, Clinical Program, will present our solutions for analysis and interpretation of cell free DNA.
Monday March 21, 2016 at 09:30 - 10:30 AM EST
Register now
By signing up you’ll automatically be able to attend all webinars in this 4-part series on cfDNA.
