Abstract 2960
Background
A new multiplexed biomarker panel is being developed for detection of microsatellite instability (MSI) that is more sensitive than currently available systems. Preliminary research data shows increased MSI sensitivity for colon polyps and endometrial (EC), skin and prostate cancers. The sensitivity of this Pan-Cancer MSI System is being further verified on 14 different cancer types.
Methods
Selection of the new microsatellite biomarkers was done by screening 160 patients ≤55 years with ≥1 polyp and 100 EC patients ≤ 50 years for MSI. The expanded study uses samples from 100 Lynch syndrome colorectal cancers (CRC), 100 sporadic MSI-High CRC, 100 sporadic MSI stable CRC and 219 extra-colonic cancers obtained from the Colon Cancer Family Registry. DNA samples are being tested for MSI using two pan-cancer systems: Promega’s MSI Analysis System version 1.2 and the improved prototype Pan-Cancer MSI System. Mutations in mismatch repair (MMR) and BRAF genes were tested, as well as MMR expression by IHC.
Results
2.3% of colon polyps were MSI-High for the MSI Analysis System compared to 5.4% with the new prototype Pan-Cancer MSI System. Sensitivity and specificity of the new biomarker panel for detection of MMR deficient lesions was 100% and 96%. Similarly, sensitivity of the new biomarker panel for EC was about 2-fold higher. Allele size changes for MSI-High samples were significantly larger with the new biomarkers making MSI classification highly accurate and robost. The MSI and IHC results were highly correlated. Evaluation of the new biomarker panel is being performed on over 500 cancer samples from 14 different cancer types.
Conclusions
Research results indicate that MSI sensitivity for colonic polyps and many extra-colonic cancers can be increased by at least 2-fold over current MSI systems using the new MSI biomarker panel. The improved sensitivity of the Pan-Cancer MSI System should improve detection of MSI in an expanded number of cancer types and facilitate identification of individuals with both sporadic and hereditary MSI-High cancers.
Clinical trial identification
Legal entity responsible for the study
Promega Corporation.
Funding
Promega Corporation.
Editorial Acknowledgement
Disclosure
J. Bacher: Employee: Promega Corporation. R. Halberg, P. Ward, K. Murphy, J. Eshleman: Corporate sponsored research funds: Promega. E. Udho, M. Uhr: Employee: Promega. D. Storts: Employee and stock ownership: Promega. All other authors have declared no conflicts of interest.