Fusion Transcript Analysis: CeGaT Enables a New Dimension in Tumor Diagnostics

CeGaT GmbH is expanding its tumor diagnostics with a new panel to detect gene fusions at the RNA level. Thus, CeGaT makes an essential contribution to the selection of the best therapeutic approach. The fusion transcript analysis enables the detection of predefined relevant fusions and gene fusions whose exact partners or fusion breakpoints are unknown. Our latest highly sensitive RNA-based analysis approach detects significantly more clinically relevant fusions than DNA or whole transcriptome analyses.

In particular, the research field of gene fusions in solid tumors has become increasingly important in recent years, both in diagnostics and in therapy. For example, there are highly effective drugs for patients with NTKR fusions. The drug Larotrectinib was the first cancer drug to be approved for all tumors with NTKR1 fusions, regardless of tumor entity.

CeGaT has, therefore, developed a diagnostic RNA-based fusion transcript analysis. This analysis allows detecting gene fusions and selected intragenic structural variants that may influence tumor development and the associated treatment decisions.

The fusion transcript analysis of CeGaT on RNA basis includes:

  • 106 genes for which a fusion with an unknown partner is also detected
  • 85 targeted breakpoint enrichments of known and described fusions
  • 5 specific therapy-relevant transcript variants

RNA-based fusion transcript analysis detects many more clinically relevant fusions than DNA or full transcriptome analysis.

The fusion transcript analysis is superior to DNA-based detection methods and approaches based on whole-RNA sequencing. To gain a complete understanding of the genetic makeup of the tumor and thus be able to make the best possible therapeutic decision, it is highly recommended to extend genetic tumor diagnostics by fusion transcriptome analysis.

CeGaT’s vision is to make comprehensive diagnostics based on the latest research results accessible and, as a result, to offer a high-quality and always up-to-date basis for therapeutic decisions. To ensure high quality and flexibility, all steps at CeGaT are performed in-house.

Further information on the fusion transcript analysis is avaliable here.

Update and Extension of Tumor Diagnostics

Diagnostics based on the analysis of tumor tissue plays an increasingly relevant role in the treatment of patients with tumor diseases. The more comprehensive the diagnostics, the faster the treating physicians receive all the information relevant for therapy decisions. Time is crucial for the patient, and the highest possible quality must be guaranteed.

CeGaT has many years of experience in the field of tumor diagnostics. Based on the latest scientific findings, the company has now expanded and optimized its comprehensive panel for Somatic Tumor Diagnostics (TUM). The panel is used to identify somatic changes in the tumor genome that are different for each tumor and that significantly influence the effectiveness of drugs and drug resistance. The findings from somatic tumor diagnostics are the basic prerequisite for targeted treatment.

Maximum information about the tumor with only one test

CeGaT’s somatic tumor panel now comprises 766 genes on 2.25Mb coding sequence (1Mb = 1 megabase = 1 million positions of genome). Tumor and normal tissue are sequenced in parallel (2X 2.25Mb). To detect subclonal variants, for example, in a liquid biopsy, we sequence at a high average sequencing depth (500-1,000x). For treating physicians and interdisciplinary tumor conferences, the most relevant aspect are germline changes in DNA repair genes (mismatch and homologous recombination deficiency), tumor mutation burden (TMB = Tumor Mutational Burden), HRD (homologous recombination deficiency) in the tumor, driver fusions, copy number changes, and driver mutations.

To our knowledge, there is currently no other tumor diagnostic that is more diagnostically sensitive and comprehensive. We want to offer the best product on the market for our patients and cooperating physicians. We have the highest standards and are not only nationally accredited (by the DAkkS) but also internationally (by CAP/CLIA).

Testing for heredity of tumor disease and pharmacogenetics is a central component of our diagnostics

The detection of inherited and thus possibly disease-causing variants in the genes is essential for therapy decisions and also for accompanying the affected patients. Aftercare can also mean prevention, and predispositions must therefore be recognized in time.  Every fifth tumor develops based on an inherited predisposition. This knowledge is as relevant for the therapy of the affected patients as it is for predictive diagnostics in healthy family members.

Furthermore, genes that are of direct importance for the metabolism of drugs are analyzed (pharmacogenetics, PGX). In this context, variants can lead to a considerably increased toxicity of drugs. This fact should be recognized before starting a therapy to spare the patient considerable side effects. If therapy-relevant changes in PGX genes are found, these are listed in the medical report.

Option for an extended medical report with clinical studies and re-evaluation

CeGaT offers not only a compact medical report with all essential information but also an extended version of the report. In the extended version, we provide information on the biological function and prevalence of the detected variants as well as a detailed description of possible treatment options, combination therapies, and possible resistance mechanisms. The report is supplemented by an individualized list of eligible FDA- and EMA-approved drugs.

CeGaT’s diagnostic services also include the regular re-evaluation of our findings against the background of new scientific findings or newly approved drugs, which can be requested at any time and is available free of charge. We also re-evaluate variants of unclear clinical significance (VUS) in order to ensure that families are cared for throughout the course of the disease and also to increase the diagnostic clarification rate in the future.

For further information, please do not hesitate to contact us personally or at sales@cegat.de. Our diagnostics can be requested here.

CeGaT’s Genetic Tumor Diagnostics: Significantly Enhanced Medical Reporting

CeGaT has updated its Somatic Tumor Panel: Sequencing of 742 genes in tumor and normal tissue, reporting of treatment option, TMB and MSI determination, illustration of tumor-relevant signaling pathways. This helps physicians to identify the best therapeutic strategy.

Every tumor has an underlying genetic cause: a unique set of mutations that help the tumor to survive, reducing its sensitivity to treatment and developing resistance against drugs. Knowing a tumor’s mutations helps to identify promising therapeutic strategies and to avoid ineffective treatment options with their associated side effects. The goal of our Somatic Tumor Panel is to analyze all genes known to be involved in the development and progression of a tumor and to make this information accessible by means of a comprehensive and actionable medical report.

Our medical report on somatic tumor mutations features a wide range of analyses that offer physicians a detailed understanding of the molecular changes within the tumor cells. All our analyses are designed to assist the treating oncologist to choose an individualized treatment for each patient:

  • Treatment options

Our comprehensive medical report describes which of the tumor’s somatic mutations have potential therapeutic relevance. We list all treatment options.

  • TMB/MSI determination

Reliable determination of tumor mutational burden (TMB) and microsatellite instability (MSI) is a basis for a decision on immunotherapies with checkpoint inhibitors.

  • Illustration of tumor-relevant signaling pathways

Understanding altered signaling in the tumor helps to find its vulnerabilities and allows to identify the tumor’s possible bypass strategies.

We continuously update our panel according to recent scientific publications. For this update 32 genes have been added. We now analyze 742 tumor associated genes and selected translocations in 31 genes.

To ensure the highest sensitivity, specificity, and accuracy, we base our analysis on tumor and matching normal tissue. Only this approach guarantees accurate results. To maximize diagnostic yield, we include the analysis of single nucleotide variants (SNVs), insertions and deletions (INDELs), and copy number variants (CNVs).

We also offer a liquid biopsy option: Liquid biopsy is a useful method to access tumor tissue if it is not possible to obtain tumor tissue through surgery.

Sequencing, bioinformatic analysis and scientific interpretation are all done in-house by our specialized team. Our laboratory is fully accredited according to CAP, CLIA and DIN EN ISO 15189:2014.

For any questions please contact our team at sales@cegat.de. The somatic tumor analysis can be ordered here.

Tumor Immuno-Oncology as an Independent Analysis with Biomarker Tumor Mutation Load (TMB) and Microsatellite Instability (MSI)

CeGaT now offers the analysis of tumor mutational burden (TMB) and microsatellite instability (MSI) as a stand-alone analysis. The diagnostic portfolio of genetic tumor diagnostics is thereby expanded with a specific test for decisions on immunotherapy using checkpoint inhibition.

Immunotherapy has become an important and promising treatment option for cancer patients in recent years. Immune checkpoint inhibition is already a frequent therapy recommendation of the Molecular Tumor Board at the University Hospital in Tübingen. Its relevance to medicine and society has also been recognized by the Nobel Prize Committee, which has awarded this year’s Nobel Prize for Medicine to James P. Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation.

CeGaT supports oncologists in carrying out this innovative therapy option in clinical practice. CeGaT’s TMB analysis has been available since 2017, as a part of the Somatic Tumor Panel for Treatment Decisions. Offered as a stand-alone analysis, the TMB diagnostics is now available with shorter turnaround times, improved cost-efficiency, and features our industry-leading high quality.

TMB as a predictive tumor marker for immuno-oncology

The benefit of immunotherapy using immune checkpoint inhibitors is undeniable, yet success rates still vary. Despite the same diagnosis, some groups of patients respond better to immunotherapy than others. Therefore, there is a need to identify and standardize new biomarkers for the identification of groups of patients that respond well to immunotherapy. One of these biomarkers is tumor mutation burden (TMB).

A growing number of studies are providing evidence that tumor mutational burden (TMB) is a good marker for treatment of tumor patients. It is defined as the number of somatic mutations per million base pairs (Mut/Mb). High TMB is associated with an increased response to therapy with immune checkpoint inhibitors.

High-quality determination of TMB is the basis for therapeutic decisions on checkpoint inhibition and should be regarded as part of routine diagnostics in tumor therapy.

The CeGaT TMB analysis can be requested here:

Tumor Immuno-Oncology Analysis (TMB and MSI)

For further assistance please contact our team at sales@cegat.de.

Panel Update: Tumor Diagnostics

In accordance with the latest scientific findings, we are updating our somatic tumor panel. The total number of genes on this panel is now 710, up from 649. The panel now includes mutational load analysis of the tumor and also supports the examination of leukemia and lymphoma.

The current update was designed to enable personalized therapy decisions, determined by an interdisciplinary tumor board, addressing solid tumors, leukemia and lymphoma. We’ve added additional genes that, according to the latest scientific findings, are linked to the development, growth, disease outlook, drug metabolism, and tumor therapy outcome. The examination of selected translocations is now performed in 29 genes.

In addition to the reporting of these treatment-relevant gene changes, we are also expanding our medical reports by reporting the mutation load of the tumor. Data increasingly suggests that tumors with very high mutation load have increased numbers of neo-antigens on the cell surface, and may therefore respond particularly well to immunotherapeutic approaches, such as checkpoint inhibitors.

In the context of genetic counseling, it is also possible to carry out tumor diagnostics by performing a liquid biopsy (blood test). If you would prefer this option, please arrange a personal appointment.

In parallel to these changes, we have also updated our panel for the diagnosis of hereditary tumor diseases by expanding the number of analyzed genes from 110 to a total of 124. Genes associated with increased tumor risk in gastric carcinoma, Cowden’s syndrome, as well as tumors of the central nervous system have been added. Furthermore, several indications already included in the panel have been extended by the addition of the new genes.

Somatic Tumor Panel