Microsatellites are regions of DNA repeats with different lengths, i.e., instability, highlighting DNA mismatch repair gene deficiencies. Typical lengths for these DNA repeats are between 1-6 base pairs and vary person to person such that each person has a set length of these microsatellites in their genome. Measurements of MSI have traditionally been performed using qPCR/CE analysis methods, but new methodologies are now available that includes digital droplet PCR (ddPCR) as well as Next Generation Sequencing (NGS). Microsatellite instability status has been linked to favorable outcomes in I-O treatment response by patients with diseases such as Lynch Syndrome and colorectal cancer. Hence MSI measurements have become an important biomarker in immuno-oncology therapeutics.
LGC SeraCare has developed microsatellite instability (MSI) reference materials containing the key mono- and dinucleotide biomarkers typically analyzed in molecular MSI assays – NR-21, NR-24, BAT-25, BAT-26 and MONO-27. These markers are blended at two different allele frequency levels – AF5% and AF20% - to support MSI assay LoD determinations and accurate MSI detection. These products are offered as tumor-normal matched pairs, with variants precisely quantitated by digital PCR as well as qPCR/CE against a highly characterized genomic DNA from a background WT cell line (GM24385) determined as microsatellite stable (MSS).
FEATURES AND BENEFITS
Plasmid-based spike-ins of 5 key MSI biomarkers typically analyzed in molecular assays that measure MSI in cancer patent samples
Offered as tumor-normal matched pairs per AF level
Each biomarker blended at two AF levels – 5% and 20% - to support assay LoD determinations and accurate MSI detection in patient samples
Variant AFs quantitated by ddPCR and qPCR assays
Normal background DNA is a highly characterized GM24385 human genomic DNA known to be microsatellite stable (MSS)
Manufactured within cGMP compliant and ISO 13485 certified facilities
1There is ambiguity in the literature on the MONO-27 locus so two constructs are included in the product to ensure compatibility (see Bacher J, Halberg R, Kent-First M, Wood KV. “Methods and kits for detecting mutations” US Patent US20090068646A1 issued March 12, 2009; and Pino MS, Chung DC. “Application of molecular diagnostics for the detection of Lynch syndrome.” Expert review of molecular diagnostics vol. 10,5 (2010): 651-65. doi:10.1586/erm.10.45).