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>Sgt; David Main is Director of the Cancer Genetics Program at the hospital for sick children, and he is a Professor of Pediatrics at the University of Toronto. And David will speak to Li-Fraumeni syndrome, TP53 and beyond. [Background Sounds] >> David, thank you very much and thank you also to Steve and all the organizers. This is, as Louise said, an incredible honor and pleasure to be here to pay tribute and honor to Doctor Fragment, and I think also by association to Doctor Li. This has been for me a wonderful run since I had the opportunity to work with Fred, with Steve Friend, and then of course, with Doctor Fragment and others and Louise on this remarkable syndrome. And it also really established my career, both in science and medicine. But I think also most importantly I recall after our paper that we went out for dinner with Fred and Elaine, Steve and his wife, and Fred flew my wife down from Toronto. And we were having a nice dinner and decided to toast something. And Fred actually said, “You know, we're going to toast friendship. Because at the end of many years from now, we won't really remember if the mutation was a codon 248 or 273, but we'll still be friends.” So, I'd like to say that. So I'm going to run through a number of slides. And I realize that I probably have way more than my allotted time. So as Steve said, if you have a minor seizure disorder, please look away occasionally to recalibrate your neurons. The way to study these syndromes nowadays that were relatively rare, but I think today are becoming much more common are through international consortia. So we've established the Li-Fraumeni Syndrome Exploration Consortium. E being for the life and for the life of us we couldn't figure out what to call E. But Jeff Wentzel came up with this, and we've tried to establish it to enhance the collaborations that we have. The second important piece here is our Brazilian colleagues. And Brazil has a particularly high incidence of germ line P53 mutations, carried at a rate of about 1 in 300 perhaps. And this is an example of one of these families with their very, very extensive pedigree. And the key individuals here, Maria Isabel Schatz, Patricia Trolley who is in Porto Alegre, and then Pierre Renault who's in France and a wonderful molecular epidemiologist. And one of these classic families. And the reason I put it up aside from acknowledging them as well, and this is a family, is they've collected DNA, all the individuals in red have collected DNA going back about six generations that we and they have been collaborating on a variety of studies, which I'll touch on. But also, as Pierre has noted, by looking at the database out of ARC on p53, there's some interesting observations that these Brazilians have taught us. This is actually not from the Brazilian database, this is actually the general database. And we know that in the Li-Fraumeni syndrome there sort of appear to be three phases. There's this very, very high incidence of...

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