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Published on: September 25, 2011
Automated, multiplex assay for high-frequency microsatellite instability in colorectal cancer
1Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.
Summary
A new three-marker microsatellite instability (MSI) assay accurately identifies high-frequency MSI-H colon cancers. This multiplex assay identifies a smaller MSI-H group with better prognosis, suitable for HNPCC screening.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Hereditary nonpolyposis colorectal cancer (HNPCC) diagnosis relies on microsatellite instability (MSI) detection.
- Current National Cancer Institute (NCI) recommended markers show variable sensitivity for high-frequency MSI (MSI-H).
Purpose of the Study:
- To evaluate individual microsatellite marker sensitivities for MSI-H detection in HNPCC.
- To develop and validate a more accurate multiplex assay for MSI-H identification.
Main Methods:
- Assessed sensitivity of five NCI-recommended microsatellite markers in 18 HNPCC tumors.
- Developed a three-marker multiplex polymerase chain reaction (PCR) assay.
- Validated the multiplex assay and NCI assay in 120 early-onset colon cancer patients.
Main Results:
- BAT25 and BAT26 showed 100% and 94% sensitivity for MSI-H detection, respectively.
- The three-marker multiplex assay identified MSI-H in 16% of early-onset colon cancers, compared to 23% by the NCI assay.
- Multiplex assay identified a more homogeneous MSI-H cohort with significantly better 5-year survival (100% vs. 44%).
Conclusions:
- A three-marker multiplex assay accurately identifies MSI-H colon cancers.
- This assay identifies a clinically distinct MSI-H subgroup with a favorable prognosis.
- The multiplex assay shows promise for HNPCC screening and prognostic evaluation.

