 It's wonderful to be here and I would like to start by saying that I think we can only move forward with, you know, the research in the area of Lieferman syndrome if we do it together with the families and the affected individuals. And therefore I think it's so great that so many are here today. And I'm also proud to be the new chair in Germany of the newly founded LFSA Germany branch. So we just have, I'm going to talk about that a little bit a little later. So I'm a pediatric oncologist and I'm very interested in syndromes that predispose to cancer and the reason is simple, it's the only really known cause of childhood cancer. Therefore I find it's irrelevant. And today we believe that at least 10% of all children with cancer have an underlying genetic predisposition. And more important for this meeting today of the 100 genes that are in this 10%, P53 is the most relevant. And there's a recent study published in Nature from the German group and or by the German group and they estimated that 1.5% of all cases of childhood cancer are due to a germ limitation of P53. So in Germany we have 2100 cases of cancer each year that means that there are 300 cases or children with cancer who have an underlying germ limitation of P53. Why is it relevant to identify these patients? It's so relevant because it matters in terms of therapy, surveillance, risk reduction or prevention and family counseling. And if you don't recognize it, you just deliver the regular therapy for these individuals. The problem in Germany, I told you earlier that we have 2000, roughly 2000 cases. We have too many centers. In Holland right now they only have one center. We have 60. And that is good for the families that don't have to travel so far. However, I'm pretty sure that not many physicians know about Liefermane syndrome and in order to increase the awareness, Stefan Fister, his name was came up often already earlier and I have recently found a cancer predisposition working group just to increase the care for these individuals and children with cancer who have an underlying predisposition. And one of the first and low hanging fruits was to make sure that the obvious cases would be recognized. And what do I mean by obvious? I mean obvious in terms of the family history, which was frequently overlooked. The histology, for example, Adrenocortical Casinoma or Choreoplexus Casinoma, you have to test for Liefermane syndrome. The somatic signature, David gave the example of Chromatripsis and Medulla Blastoma and the physical features. And we have adopted a Dutch, or changed a little bit, a Dutch form and have created one page questionnaire and all centers that are certified for pediatric oncology are now required to use this form for each new patient just to make sure they find those who have an obvious cancer predisposition syndrome. The problem here is obvious too because it only looks for the obvious cases, the hidden cases are, by definition, overlooked using this form. And this is a big problem because many cases of cancer predisposition in children with cancer that don't have positive family history, they are basically hidden. And therefore, I'm very convinced that within the next few years we will have agnostic tests for all patients when they are newly diagnosed. And just to give you one example why this is so relevant from the brain tumor field. There's a recent paper that came out and David was one of the major players on that paper too, it lands on oncology. It's about Medulla Blastoma. And this paper showed that 25% of the older children with sonic head shock Medulla Blastoma aged 5 to 14 years have an underlying germline mutation of P53, 25%. And another 20% of the younger children up or below the age of three with sonic head shock Medulla Blastoma have an underlying germline mutation of Zufu. And yet another 7% of patients with wind activated Medulla Blastoma have a germline mutation of APC. And most of these patients were cryptic so they were not identified clinically, they were only identified by sequencing. And therefore, this is a nice example why this is so relevant. And we are currently planning a study to convince the insurance companies to pay the sequencing up front by comparing the clinical and the agnostic testing just to show that we would miss many of these patients by just using the clinical easy survey. And I'm convinced that when we identify the patients that have a syndrome and we are able to do or to individualize the treatment, conduct surveillance and so on, we will save so much money that we can easily pay for the sequencing. But we will also look for the costs in the study and also conduct a psychosocial assessment. The surveillance in Germany, we recommend it in a quite simple manner, we simply use the AACR guidelines, but we are aware of the fact that the guidelines they have been talked about many times already today, they will change over time. And I'm very happy that there is so much going on right now that they will eventually change so they can be adopted according to risk. Right now, this is not the case. So whenever you have make recommendations like surveillance for all the different syndromes, it's important to also create data to see whether it's effective or not. And for that purpose, Stefan Fister and I have recently launched a registry for patients with Li-Fromini syndrome in Germany. And because Li-Fromini syndrome is not alone, there are hundred other genes beside P53 and 60 other syndromes, and it wouldn't be effective to open 60 different registry, we just decided to open one registry, a cancer-prone syndrome registry. And that patients with drumline mutations of various genes and oops, so we decided to put all the syndromes into one protocol, the cancer syndrome protocol. And so what we have also done is to create a platform, an information platform, and this information platform is called, I mean I just continue, it doesn't really matter. It's called FIT, which stands for effects and investigation therapy. It has information on 60 different syndromes for all the families, so very easy to understand. And all the 60 syndromes for professionals, and also information on different tumors, and then you can click on the different tumor types, and you can see the syndromes that are associated with these tumor types. So it really helps for the daily practice for families and for professionals to learn in a very efficient, fast way about these syndromes. And the website is cancer-prudisposition.org, and we are currently translating it in different languages. We started in German, next language is English, but then we will go to different languages. We do have DTAs, data transfer agreements and material transfer agreements with other registries in place. For example, with the registry of the live consortium, I think it would be also very important to be able to talk with the French registry, because I mean we need to work together with the families and the different registries in order to move forward more quickly and in a more efficient manner, and not to do a MeToo initiative. We have to really work together. And for that reason, we had recently a meeting in Brussels because we want to somehow in Europe to incorporate all the different various activities from the various registries and have a joint data collection within Europe, and this is likely to happen under the umbrella of SIOP, and this will also include Israel as well, and we just had a first meeting recently in Brussels. And there's a nice picture that I cannot show you, but tell you about, about all the people who are standing at Brussels airport. So the last topic is the treatment part, and the treatment part is a little bit embarrassing, because we, I mean there's a lot happening right now, but despite the fact that a leaf from any syndrome was discovered 50 years ago, we are still not diagnosing all patients and we don't know really how to treat them, and the problem is very simple, no we can see it again, it doesn't matter, the problem is very simple, conventional chemotherapy and radiation therapy tries to, or destroys DNA and that leads to apoptosis of tumor cells and that requires P53 in order to happen. And in patients with leaf from any syndrome, there is likely to be more toxicity, for example secondary neoplasm, and there is more likely to be resistant. I think it doesn't matter, I mean there is likely to be more resistance, and the resistance is very easy to understand, because the tumors require P53 in order to die with chemotherapy. And therefore we need new ways to treat these patients, and this is not, by the way, not only true for all patients with leaf from any syndrome, this is very, very similar in many other disorders with an abnormal DNA damage response, there are different diseases including dyscaratosis, including funcone anemia, including, no you took it away from me here, so many, there is a range of conditions that have an abnormal DNA damage response, and they are all, all these conditions including nymeving breakage, Werner syndrome, ligase 4 deficiency, mismatch repair deficiency, seroderma pigmentosum, they all have a tremendous risk of developing cancer, and yet we don't really know how to treat patients with cancer, because they have such a high rate of toxicity. And for that reason we are creating a new project right now in Germany called Address, and the address stands for abnormal DNA damage response, and this is something that can really only work with the families, because we require the families to work together with the registries, with the physicians, otherwise the tumors that we can study in order to discover new treatment options, there are some are lost in the different hospitals, and we really need every single patient to collaborate here in order to be very, very efficient, because the idea is to take every tumor that arises in a person with Lyftomania syndrome, bring it into the lab, create a mouse model with these patients or with these tumors, and treat them ex vivo and try to find therapies that work in the mice, and then after identifying new therapies, bring them into clinical trials. And I think in this type of work, the families and the family organizations are really the key because it wouldn't work without them. And for that reason I'm very convinced that the progress of the field in Lyftomania syndrome wouldn't be happening so efficiently without organizations like the Lyftomania Association, and I was very honored two years ago when Jen Perry, I think she's going to speak during this meeting also, and Holly from INE approached me, and we were able to launch a branch now in Germany. We recently had a first Lyftomania meeting which was very similar to this one here, a first LFSA Germany branch meeting, and here are some nice pictures. I can tell you, I can describe them, a very, very nice group picture of the families. We also went to the zoo and saw the elephants, which was inspired by Josh Schiffman's work on Elephant P53, and we had a fantastic time. I think at that point I would like to finish. It's also a little bit difficult to project here, but no problem, and I would like to thank all the members of the Lyft Consortium, many of them are here today, especially I would like to thank Thierry for your very kind invitation, I'm very happy to be here today. I would very much also like to thank Jen Perry and Holly from INE, they are the drivers from the patient side, and without their power I think many things just wouldn't happen, and I'm very thrilled that now there's also going to be a chapter here in this country. It's going to be very nice, and I look forward to collaborating closely with you, and finally here is a picture of my team, very nice people, very good looking people, and thank you for inviting me. It's wonderful to be here, bye. So sorry for the technical problem, so what I decided to do is to make the break, so we're going to fix it, and after that you are going to show the slides, especially with your team because that's very important, right? So we changed the program and we'll make the break right now in order to fix for the last speakers. I think what is very impressive is what the registry, right? So my question to come back to the patient, so ask what we are doing because this morning was a discussion, and Laurence nicely had a question, which type of patient should we test? So as of present time, so in Germany are you systematically offering German IPv3 testing for children presenting the typical LFS tumor that you know very well, or are you going to systematically offer a German line to offer an indication? So right now it's the first, so we just, so until just five years ago the adrenal cortical carcinomas were not tested, and the chord plexus carcinoma were not tested because it was just simply ignored. I mean we now from the work from Sharon, Savage, that roughly 10% of osteosarcoma patients have a variant, but when you ask the guy who runs the osteosarcoma registry, he doesn't know any patient with leaframine in his osteosarcoma registry. So it was simply ignored until, despite the fact that so much is already known, and now we are, so what we are doing now, we test it for all the obvious ones, the chord plexus, and the hyperdiploid ALL, and so on, and the sonic hedgehog medullos. So that's the case right now, and we do it very consequently, and by doing so we pick up many, and then we also have another thing in Germany that's called the inform study that is run by Stefan Fister, and they sequence all the relapse cases of cancer independent of the diagnosis, and they pick up a lot of variant carriers also, so they will be included in the registry also. And because there's also no registry for adults, we will also include adult cases in the registry as well. So in other words, like in different countries, there is a need to diffuse information, I think I say the request from the patient side, so from as an additional that probably many people, especially people walking in the MRI, radiology, oncology are not very familiar with that. And I think this is the big problem that we are not really advanced in the therapy. We are very advanced in Down syndrome because it's written on the forehead that you have Down syndrome. You can easily diagnose this. In Liefermini syndrome, it was ignored for the last five decades, therefore we have to do our homework starting now because we have no clue how they do compared to the other ones. So we need to consequently diagnose them, and then we have to do trials for patients with Liefermini syndrome. Okay. So I will propose since we are lucky we have... You know, don't worry about my slides. I mean, we need to move forward with the time, so it really, I don't really mind. So that's our team. That's our team. Yes. You have two seconds to present them. Yeah. No, so yeah. So that's our lovely, lovely team.