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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

2960 - Development of a Pan-Cancer Biomarker Panel for Improved Detection of MSI Across all Cancer Types

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Jeff Bacher

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

J. Bacher1, R. Halberg2, P. Ward3, E. Udho1, K. Murphy4, M. Uhr5, L. Dubeau3, J. Pettersson3, D. Storts1, S. Gallinger6, D. Buchanan7, M. Jenkins7, N. Lindor8, J. Eshleman9

Author affiliations

  • 1 Rd Nucleic Acid Technologies Group, Promega Corporation, 53705 - Madison/US
  • 2 Department Of Medicine, University of Wisconsin-Madison, Madison/US
  • 3 Usc Keck School Of Medicine, University of Southern California, Los Angeles/US
  • 4 Pathology, ProPath, Dallas/US
  • 5 Rd Protein & Nucleic Acids, Promega Corporation, 53705 - Madison/US
  • 6 Mount Sinai Hospital, University of Toronto, Toronto/CA
  • 7 Melbourne School Of Population And Global Health, The University of Melbourne, Melbourne/AU
  • 8 Health Science Research, Mayo Clinic, Scottsdale/US
  • 9 Pathology, Johns Hopkins University, Baltimore/US
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Resources

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.

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