Modaplex MSI Analysis Kit
The Modaplex MSI Analysis Kit is a PCR-based multiplex assay for the qualitative assessment of microsatellite instability. With a set of seven microsatellite markers (Bat-25, Bat-26, NR-21, NR-24, Mono27, D5S346, D17S250), the kit detects instability by comparing microsatellite profiles from cancerous and normal matching tissue. The set of seven markers allows for the individual assessment of MSI-High status based on established and standardized guidelines using a combination of mono and dinucleotide markers or mononucleotide marker only.
The Modaplex MSI Analysis Kit is intended for research use only purposes and not for diagnostic use.
|Targets||Mono nucleotides: Bat-25, Bat-26, NR-21, NR-24, Mono27
Di nucleotides: D5S346, D17S250
|Kit content||All reagents required to perform PCR are part of the Modaplex MSI Analysis Kit
• MSI Primer Mix
• MSI Positive Control
• Polymerase P
• PCR Buffer 10
• Modaplex Calibrator 2
• Nuclease-Free Water
|Sample Material||The Modaplex MSI Analysis Kit is verified with artificial material and tested with FFPE colorectal and endometrial cancer samples.|
|Input||Optimum: 10ng DNA|
|To be used with||Platform: Modaplex instrument version 1.0 or higher
Software: Moda-RA version 1.2.2 or higher
The Modaplex MSI Analysis Assays is to be used with the Modaplex instrument platform version 1.0 or higher. Thus, the MSI workflow is similar to the workflow of other Biotype Modaplex assays such as POLE Mutation Analysis Assay and comprises the same three steps after nucleic acid preparation: PCR set up, Modaplex run and result interpretation.
MSI as Research Marker for Immune checkpoint Inhibition
In recent years, immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of patients with advanced cancer and ICIs have become a strong pillar in cancer treatment . However, understanding the molecular biological background is still required when considering the best indication for ICI . In this context several studies have demonstrated that MSI status, as a surrogate for a defective mismatch repair system (dMMR), is a positive predictor for the response to immune-checkpoint inhibitors [3,4,5]. Furthermore, since 2017 several IC-therapies have been approved by the US Food and Drug Administration (FDA) or EMA considering the tumor´s MSI status.
As the MSI status is a practical marker, clinical researchers are currently investigating MSI and its implications for predicting the response to immune checkpoint blockade in a variety of tumor entities .
Investigate microsatellite instability in endometrial carcinoma
The Cancer Genome Atlas Research Network (TCGA) performed an integrating genomic, transcriptomic and proteomic characterization of endometrial carcinoma. Exome sequence analysis revealed four groups of tumors .
Group 1 (7% of tumors) carcinomas have somatic inactivating hot spot mutations in the POLE exonuclease domain and a very high mutational burden (ultramutated).
Group 2 (28% of tumors) include endometrioid carcinomas with microsatellite instability (MSI) (hypermutated), frequently with MLH-1 promoter hypermethylation and high mutation rates.
Group 3 tumors (39% of endometrial carcinomas) include endometrioid carcinoma with low copy number alterations, and low mutational burden, while lacking POLE mutations and MSI-H.
Clinical researchers are now attempting to bring the TCGA molecular-based classification into clinical practice . Thus, several studies investigate the performance of different MSI approaches to evaluate the suitability of approaches for endometrial carcinoma.
1. M.A. Postow et al, “Immune Checkpoint Blockade in Cancer Therapy”, Journal of Clinical Oncology, vol. 33, no. 17, pp. 1974-1983, 2015.
2. R.W. Jenkins et al, “Molecular and Genomic Determinants of Response to Immune Checkpoint Inhibition in Cancer”, Annu. Re. Med., vol. 69, pp. 333-347, 2018.
3. D.T. Le et al, “PD-1 Blockade in tumors with Mismatch-Repair Defi ciency”, N. Engl. J. Med., vol. 372, pp. 2509-2520, 2015. 5 D.T. Le et al, “Mismatch-repair defi ciency predicts response of solid tumors to PD-1 blockade”, Science, vol. 357, no. 6349, pp. 409-413, 2017.
4. V. Lee et al. “Mismatch Repair Deficiency and Response to Immune Checkpoint Blockade.” The oncologist vol. 21,10 (2016): 1200-1211.
5. Y. Eso et al. “Microsatellite instability and immune checkpoint inhibitors: toward precision medicine against gastrointestinal and hepatobiliary cancers.” Journal of gastroenterology vol. 55,1 (2020): 15-26.
6. J. Tang et al. “Trial watch: The clinical trial landscape for PD1/PDL1 immune checkpoint inhibitors.” Nature reviews. Drug discovery vol. 17,12 (2018): 854-855.
7. Levine, D., The Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature 497, 67–73 (2013).
8. Concin N, Matias-Guiu X, Vergote I, et al ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma International Journal of Gynecologic Cancer Published Online First: 18 December 2020.
Would you like to receive more information on how simultaneous MSI and POLE testing with Modaplex can streamline your research activity? Contact us at: firstname.lastname@example.org
|Product:||Modaplex MSI Analysis Kit|
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