Functional analysis of the novel MLH1·ITGA9 fusion protein of a Lynch syndrome family

We have investigated a Lynch syndrome family and identified a novel mutation of the mismatch repair gene MLH1. Apart from already described point mutations or gene deletions, we identified the first genetic gene fusion of the MLH1 gene. The gene fusion was generated by an interstitial deletion on chromosome 3p21.3 that deleted three genes and led to the fusion of MLH1 (exons 1–11) and ITGA9 (exons 17–28). The fusion gene is translated into a functional fusion protein that confers oncogenic properties on transfected mammalian cells. Thus, this novel mutant of MLH1 does not only provide a loss-of function (mismatc…