OR06: DiagMMR: Functional Lynch syndrome carrier testing from skin

Minttu Kansikas1, Jukka Kantelinen1, Mariann Kasela1, Pauliina Paloviita1, Jukka-Pekka Mecklin2.3, Päivi Peltomäki4, Minna Nyström1,5,

1 – LS CancerDiag Ltd., Helsinki, Finland. 2 – Department of Surgery, Central Finland Health Care District, Jyväskylä. 3 – University of Eastern Finland, Finland. 4 – Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland. 5 – Department of Biosciences, University of Helsinki.

Aim

Our aim is to optimize the specificity and sensitivity of the predictive DiagMMR functional test for Lynch syndrome (LS) diagnostics.

Method

The DiagMMR method recognizes reduced DNA mismatch repair (MMR) by quantitatively assessing the MMR efficiency of cells derived from normal skin tissue and hence allows inherited cancer predisposition to be diagnosed from healthy LS mutation carriers without mutation sequencing.

Results

Using samples obtained from known LS mutation carriers and their unaffected family members, the DiagMMR method has been optimized to distinguish MLH1, MSH2 and MSH6 mutation carriers from non-affected individuals. The clinical validation of the test is commencing.

Conclusion

This prominent method for recognizing LS without the onset of cancer is now ready for clinical validation which can only be accomplished with the broad support of LS clinicians, as LS mutation carrier skin samples representing a variety of different MMR-gene mutations is required. In order to apply the DiagMMR test to the clinical screening of LS carriers a rigorous validation of the method needs to be completed.

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