Center for Genomic Medicine: A true Sample to Insight laboratory
09/09/2015 // Feature // Text: Rod Hise

Transforming advances in genomics into better diagnostics and treatments for patients.

“Most people I meet are surprised by the extent to which genomics has already changed healthcare,” said Professor Finn Cilius Nielsen, head of the Center for Genomic Medicine at the Rigshospitalet in Copenhagen.

Indeed, recent years have seen a dramatic change in the way medicine is practiced. These changes are driven by new genomic insights, improved screening and diagnosis of disease, and, even more importantly, treatments tailored to the genetic makeup of individual patients to improve their outcomes – a concept that is now widely known as personalized healthcare.

The anticipation of these changes was the genesis of a new laboratory established in 2010. “Back then, we saw genomic medicine rapidly making inroads into clinical practice and wanted to ensure that the hospital has access to the latest technologies to enable state-of-the-art care for our patients,” recalls Professor Nielsen, who started the lab with a dozen employees.

To this end, the laboratory employed a two-tier structure: a research arm to evaluate the potential of emerging technologies for routine use, and a clinical diagnostics arm that puts these technologies to use in routine practice. As a result, Professor Nielsen’s laboratory has quickly become one of the world’s leading institutions in developing genomic technologies into routine clinical applications.

The center runs up to 3,500 genetic tests a year with a staff of 40. The tests are mostly performed on advanced next-generation sequencing (NGS) and microarray technologies. “We are applying these technologies to clinical practice more quickly than anyone anticipated,” Professor Nielsen said. Most are used to improve cancer treatments.

“We are applying genomic technologies to clinical practice more quickly than anyone anticipated."
Prof. Finn Cilius Nielsen, Head of the Center for Genomic Medicine at Rigshospitalet, Copenhagen
The focus on cancer diagnostics takes at least two forms. First, the laboratory uses microarrays to improve classification of various tumors beyond pathological examination of tissue samples. Second, the laboratory also performs sequencing for a broader picture of tumor genetics that helps to determine disease-driving mutations and assists with the development of personalized treatments.

The decision about which approach to take is dependent on the patient or cancer type. For example, sequencing of the whole genome or exome – the coding part of the genome – is primarily used to analyze suspected rare genetic disease or cancer patients not responding to regular, first-line treatments. For genetic diseases in general, sequencing results can provide the explanation for about one-third of the cases that have not been diagnosed through traditional investigations. For central nervous system diseases, up to one-half of the cases can be explained. For more specific investigations of cancer patients, i.e., for guiding treatment decisions in personalized medicine, specific biomarkers of interest are analyzed using gene panels that amplify the genes or genomic regions of interest and allow for targeted and highly efficient sequence analysis.

To ensure access to these and other cutting-edge technologies, the center maintains close relationships with leading technology providers, including QIAGEN. The two organizations recently entered a formal partnership that further strengthens their collaboration. The agreement is centered on QIAGEN’s “Sample to Insight” solutions for NGS, with a focus on cancer, and covers full workflows including reagents, instruments and advanced bioinformatics.

"The work being done at the Rigshospitalet is truly groundbreaking and a remarkable example of what can be accomplished through QIAGEN’s Sample to Insight solutions for NGS."
Kim Soerensen, Vice President, Headof Global Strategic Business Team NGS at QIAGEN (on the right).
For the initial bioinformatics analysis, the genomic medicine laboratory uses the QIAGEN CLC solution and associated tools. The Biomedical Genomics Workbench are used for the secondary analyses of data from different sequencing instruments, for example, when the raw DNA sequencing data is mapped to a reference genome, allowing for the identification of a patient’s mutations and other genomic variants.

For tertiary bioinformatics analysis – which represents the biological or clinical interpretation of the variants identified using the Biomedical Genomics Workbench – the laboratory employs QIAGEN Ingenuity Variant Analysis (IVA). The software initially filters out the high number of non-pathogenic mutations found in all patient samples, and helps to identify clinically relevant and actionable mutations linked to the disease in question. Using the Ingenuity knowledge database and a number of the software’s advanced filtering tools enables the identification of causative mutations in a very streamlined and efficient way. The tertiary analysis of whole genome sequencing results can start with millions of variants when a patient genome is first compared to a reference genome. Nevertheless, in some cases the use of a few filtering steps has allowed genomic medicine to narrow these findings to single mutations that cause rare genetic diseases.

“We are grateful for the strong partnership QIAGEN enjoys with Dr. Nielsen and his team,” said Kim Soerensen, Vice President, Head of Global Strategic Business Team NGS at QIAGEN. “The work being done at the Rigshospitalet is truly groundbreaking and a remarkable example of what can be accomplished through QIAGEN’s Sample to Insight solutions for NGS. We look forward to partnering with the Rigshospitalet for many years to come."

The Center’s research and development programs led by Dr. Thomas van Overeem Hansen are the first to use new QIAGEN technologies. One program focuses on hereditary breast and colon cancer using QIAGEN gene panels, which require smaller tissue volumes than existing methods, a critical advantage when working with scarce tumor samples. “With breast cancer, we hope to implement novel molecular classifications in first-line treatment to improve the prognosis and treatment,” explains Dr. van Overeem Hansen.


QIAGEN technologies also enable minimally invasive liquid biopsies to monitor patient response to cancer treatments. “We believe that liquid biopsies hold great promise for seeing how patients respond to certain treatments by continuously measuring the presence of certain biomarkers in body fluids,” said Dr. Lars Jønson  who heads the laboratory’s NGS center. The hospital already has analyzed blood samples from 80 patients with different kinds of cancers that did not respond to first-line treatment, with the initial data looking promising.

Dr. Jønson hopes that his team can soon transfer those results into routine testing.  “We truly are a Sample to Insight laboratory,” said Dr. Jønson. “As a result, we are bringing greater understanding to a wide range of important medical issues, particularly in cancer.”