MSI-dMMR-Portal

Overview of MSI-dMMR biomarkers (currently only available in German)

The QuIP MSI-dMMR-Portal is intended to serve pathologists as well as medical specialists of other disciplines and oncologists by providing orientation at the interface between biomarker tests and therapy. The portal includes a biomarker-based treatment algorithm for colorectal carcinoma and endometrial carcinoma thath is based on current medical guideline recommendations as well as new scientific findings.

Although it is currently only available in German, please check back periodically or sign up for our newsletter to be informed as soon as the portal is available in English.

Background

QuIP has set itself the task of accompanying pathologists in Germany and Europe in optimizing their examination results and to support them in all relevant professional and organizational activities in quality assurance.

During cell division, around 100,000 errors could occur in the body during DNA replication due to the insertion of incorrect nucleotides (mismatch) as well as insertions and deletions. In general, cells have a system of interacting proteins to repair such incorrectly replicated DNA (MMR proteins: MutL Homolog 1 [MLH1], MutS Homolog 2 [MSH2], MutS Homolog 6 [MSH6] and Postmeiotic Segregation Increased 2 [PMS2]). The mismatch repair genes are responsible for recognizing and repairing mismatches and the prerequisites for this are the formation of heterodimers. In this process, three pairs are formed: MSH6/MSH2, MSH2/MSH3 and PMS2/MLH1. The loss of one or more of these molecules affects different repeat types. In the case of MSH6, it is mainly the mononucleotide repeats, whereas in the case of MSH1 and PMS2 it is the dinucleotide repeats in particular and in the case of MSH3 the tetranucleotide repeats are affected as well. As a consequence of failure to repair mismatches, accumulations of mutations occur in the region of simple repetitive DNA sequences, termed microsatellite instability (MSI). This characterizes MMR deficient (dMMR)-based tumors, which can be either inherited as part of Lynch syndrome (LS) or more commonly (approximately 80 percent) acquired in the course of life (via methylation-related MLH1 failure).

Thus, depending on the cause, detection of such MMR deficiencies allows for cancer risk diagnosis (in LS) to be made as well as determination of optimal cancer therapy (high degree of response to immune checkpoint therapies).

The different phases of the diseases that are associated with dMMR as well as the corresponding tests are presented in a well-structured algorithm that contains detailed information regarding the respective tests, the corresponding results and the different therapy options. The portal and the associated information can be accessed directly via the algorithm. Alternatively, it is also possible to access the portal and the associated information either through a specific biomarker or through an approved active ingredient or drug.

The portal will be continuously expanded and further developed.

Data protection

Data protection in Germany prevents QuIP from publicly sharing the portal and the link to the website. Only the introduction can be seen on the portal start page, all other content is only available to medical professionals.

Registered QuIP users will automatically find a link to the MSI-dMMR Portal after logging in on the QuIP homepage. All physicians who have DocCheck access will also have access to the portal. All other interested parties without a QuIP account or DocCheck access can request access to the portal by sending an e-mail to QuIP. An access code will be provided once the requestor’s access requirements are checked.

The QuIP MSI-dMMr Portal is sponsored by Bristol Myers Squibb, Glaxo Smith Kline and MSD Sharp & Dohme.