The changing paradigm – away from a one-size-fits-all approach towards precision medicine – raises the importance of comprehensive genomic profiling (CGP) of tumor samples. CGP refers to the simultaneous evaluation of several biomarkers within one analysis. This approach not only enables detecting the most relevant predictive markers for current targeted therapies but also key immuno-oncology biomarkers, such as the tumor mutational burden (TMB) and the microsatellite instability (MSI). TMB is a biomarker that measures the number of somatic mutations present in a cancer patient’s tumor and is quantified as mutations per megabase (mut/Mb). Another key immunotherapy biomarker is the MSI, which is caused by the failure of the DNA mismatch repair system.
The application areas of CGP are manifold, with a focus on:
- Stratifying patients for the best treatment choice
- Identifying patients eligible for clinical trials
- Driving clinical research, especially in the area of immune therapy
You can choose between different products to perform comprehensive genomic profiling analysis.
CeGaT Is the Best Partner for Sequencing Your Project
Our Commitment to You
≤ 15 business days
Highest accuracy for all processes
Secure provision of sequenced data via in-house servers
Safe storage of samples and data after project completion
We provide a comprehensive and first-class project support – from selecting the appropriate product to evaluating the data. Each project is supervised by a committed scientist. You will have a contact person throughout the whole project.
Our service includes
- Detailed project consulting
- Product selection tailored to your project
- Detailed bioinformatic evaluation of your data
- Detailed project report with information about sample quality, sequencing parameters, bioinformatic analysis, and results
Benefit from our dedicated support and accredited workflows.
Explore Our Product Portfolio for Tumor Mutational Burden
We offer different TMB products to address a variety of research questions. When choosing our Tumor Immuno-Oncology (TIO) Panel, your samples are analyzed using CeGaT’s ‘Somatic Tumor Panel’. This covers more than 760 cancer-associated genes. Furthermore, 31 therapy-relevant fusions are analyzed at a high sequencing depth. The TIO Exome is based on the enrichment of our Whole Exome Sequencing product. This offers insights into more than 20,000 genes. For both products, a normal and a tumor sample are required for a tumor-normal comparison and the determination of the TMB and MSI. By choosing TSO500, the anaysis covers 523 tumor-associated genes. In contrast to the TIO products, the comparison between tumor and normal tissue is not required to determine the TMB and MSI biomarkers.
Would you like to have bioinformatic analyses performed on your data in addition to the included deliverables? Each of our products can be supplemented with further services. We are happy to advise you.
For comprehensive genomic profiling based on the analysis of liquid biopsies (ctDNA), please check our Liquid Biopsy product portfolio.
The analysis of our TIO Panel and TIO Exome products is based on the CeGaT bioinformatic pipeline for Panel Sequencing and Whole Exome Sequencing (WES) Level 5 with the cancer somatic mutation option, respectively. In addition to the files provided for Panel Sequencing and WES Level 5, you will receive the TMB and the MSI status in the project report
The analysis of our TSO500 product is based on the TSO500 (Illumina) bioinformatic pipeline. Only one bioinformatic analysis level is available for TSO500. The analysis includes the alignment of trimmed sequencing data, calling and annotation of SNVs and indels, as well as fusions. Furthermore, CNVs and the MSI/TMB status are evaluated. In addition to the data, a project report is generated.
At CeGaT, paired-end sequencing (2 x 100 bp) is performed using the Illumina sequencing platforms. If you require other sequencing parameters, please let us know! We can provide further solutions.
Gene Directory for TIO Panel & TSO500
Further Information about Tumor Mutational Burden
The tumor mutational burden, also known as TMB, is the amount of gene mutations occurring in a patient’s tumor, but not occurring in the patient’s healthy tissue. Thus, these mutations are coding, somatic mutations. The tumor mutational burden is defined as mutations per megabases (mut/Mb). It should not be confused with the variant allele frequency that only indicates the frequency of an allele. In contrast, the tumor mutational burden is the total amount of mutations per megabases in a sample. Depending on the tumor entity, the tumor mutational burden varies: some tumors do not show high mutation rates, such as the Ewing sarcoma or acute myeloid leukemia. Other cancer types, such as melanomas or lung squamous cell carcinomas, hold a high tumor mutational burden. Thus, the tumor can be classified as low, intermediate, or highly mutated using the tumor mutational burden. The tumor mutational burden is a promising predictive immunotherapeutic biomarker, for example in immune checkpoint inhibitor therapy. Such an immune therapy is especially effective in patients with a high tumor mutational burden. A higher number of tumor-specific mutations leads to a higher number of altered proteins, so-called neoantigens. These neoantigens are different from the healthy proteins, resulting in an increased difference of the tumor tissue compared to the healthy tissue.
Both tumor and healthy cells present parts of their protein content on their cell surface. These presented protein parts are also called peptides. Immune cells regularly check the peptides on the surfaces of the proteins. If the peptides are recognized as foreign, the immune system is activated. The tumor peptides, the neoantigens, are foreign to the immune system. Thus, a higher tumor mutational burden correlates with more mutations and more neoantigens that are recognized as foreign by the immune system. With a higher tumor mutational burden, the immune system is activated more easily.
Another immunotherapeutic biomarker is the microsatellite instability, also known as MSI. The microsatellite instability indicates the number of mutations in satellite regions. These satellite regions are special DNA repeat sequences. The satellite regions of the DNA are the main component of the functional centromeres, forming the main structure of the heterochromatin. A disturbed DNA mismatch repair mechanisms (MMR) can lead to genetic hypermutability in the satellite regions, resulting in microsatellite instability. The microsatellite instability is classified as stable for a low MSI score, or unstable for a high MSI score.
Do you have a question or are you interested in our service? Feel free to contact us. We will take care of your request as soon as possible.
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We are happy to discuss sequencing options and to find a solution specifically tailored to your clinical study or research project.
When getting in contact, please specify sample information including starting material, number of samples, preferred library preparation option, preferred sequencing depth and required bioinformatic analysis level, if possible.