Pediatric Cancer Predisposition Program at Siteman Kids at St. Louis Children's Hospital

Thirty percent of the approximately 12,500 children diagnosed with cancer each year may have a genetic cause for their disease.

A promising area of research in childhood cancer is genomic medicine, in which the genes of children with certain cancer diagnoses are closely examined. Advances in this field have shown that certain childhood cancers are related to specific genetic variations. Some of these same genetic changes may also cause other physical or developmental differences, and when grouped together, are considered to be a cancer predisposition syndrome.

In this segment, Dr Todd Druley explains how The Pediatric Cancer Predisposition Program at Siteman Kids at St. Louis Children's Hospital and Washington University School of Medicine seeks to identify at-risk children through genetic testing and diagnostic screenings, and can increase the likelihood of early detection and treatment.
Pediatric Cancer Predisposition Program at Siteman Kids at St. Louis Children's Hospital
Featured Speaker:
Todd Druley, MD, PhD
Todd Druley, MD, PhD, is a Washington University pediatric hematologist and oncologist at St. Louis Children's Hospital.


Melanie Cole (Host): Thirty percent of the approximately 12,000 children diagnosed with cancer each year, may have a genetic cause for their disease. A promising area of research in childhood cancer is genomic medicine in which the genes of children with certain cancer diagnoses are closely examined. Advances in this field, have shown that certain childhood cancers are related to specific genetic variation. My guest today is Dr. Todd Druley. He is a Washington University pediatric hematologist and oncologist at St. Louis Children’s Hospital. Welcome to the show. Dr. Druley, so explain a little bit about the genetics of cancer in children. Does it differ than the genetics like BRCA gene and such that we hear about cancer in adults?

Dr. Todd Druley, MD, PhD (Guest): Well thank you for having me Melanie and yes, you are absolutely right. The genetics of pediatric cancers are quite different than the genetics of adult cancers. Thankfully, pediatric cancers are rare, but our model of cancer comes from adult research and it takes many decades for a healthy adult to acquire the genetic damage that will cause a normal cell to become a cancerous cell. And the current sequencing efforts of DNA and RNA have proven that and you can find abundant acquired genetic mutations in older adults. So, why does a young child get cancer if that is how cancer is created through acquisition of many genetic mutations? These children don’t have that many. They might have one or two, but they don’t have enough for a normal cell to become a cancerous cell. So, then we are starting to look in the genetics that they are born with and how those genetic changes combine and may predispose those children to getting cancer, so they don’t cause cancer themselves, but they create a fertile environment if the children do acquire one of these one or two damaging mutations.

Melanie: So, why would a pediatrician refer to a specialist for genetic testing? What are some of the reasons for referral?

Dr. Druley: Well, the biggest one that we are seeing right now is a young adult parent, late thirties, early forties who gets diagnosed with cancer, maybe an aunt or an uncle and then the oncologist for the adult will inquire as to the family history and frequently, there is a grandparent or another relative in the prior generation who also was diagnosed or passed away from cancer early, before genetic testing was really the thing to do and so, in those instances, the genetic test of the person who is affected finds a concerning genetic change and then they say well we have all got children in this family, what about them. And that’s when we get referrals. There are other conditions that can be worrisome for an increased risk of cancer and we like those referrals as well.

Melanie: So, explain to us. Tell us a little bit about the St. Louis Children’s Hospital Cancer predisposition program.

Dr. Druley: So, we try to provide what I call the hub of the wheel. So, a lot of these children, they might have a very well-known cancer predisposition syndrome such as neurofibromatosis or Beckwith-Wiedemann syndrome or they may not. They may simply just have genetic testing that finds a genetic change that could increase their risk of cancer. But oftentimes, these kids have a variety of medical needs, whether it is through therapy services, neurology, GI, you know many different things and sometimes that can be overwhelming to these families. They are trying to coordinate many different appointments with many different therapy services or care providers and so we want to take that burden off these families and really be their one-stop shop. We can help make those referrals to the other providers. We can help provide testing and not only track the children ourselves and other siblings, but you know help with the global care for these families.

Melanie: So, speak about your genetic testing that you conduct there and a little bit of patient management. So, are there certain guidelines for referring cancer patients to genetic testing? Has that changed over the years?

Dr. Druley: Well, the battery of genetic tests that we are able to offer is increasing all the time and it is really something that we work hard to keep abreast with and I think it can be difficult for most general pediatricians to know what the latest recommendations are. We work hand in hand with pediatric geneticists to make sure that we aren’t neglecting any potentially important information or other potential causes of genetic differences for these kids. So, there’s specific genetic tests if we think we are really clear on what’s going on or there is much more diverse genetic tests that we can offer to patients and families after they have had appropriate genetic counseling to understand what the implications of that testing could mean, not only for the affected child but for the entire family and exactly how the family would use that information to inform care for their extended relatives as well.

Melanie: So, if you are introducing surveillance and early intervention, which hopefully would improve survival rates for familial cancers; are the relatives involved? Dr. Druley, do you then if a child comes in and if there is something going on hereditary, does the family get involved? Do they get tested too?

Dr. Druley: Absolutely. I think it is critical to make sure that all the full siblings in the family are tested. We have gone on to test cousins of some of these children and found families where ten or twelve people are actually affected with the damaging genetic changes and require long-term surveillance both as adults and as children so it’s really making sure that they understand this could affect their entire family and depending on the age of the affected child, they need to know that information if they are getting close to early adulthood where they may want to start family planning for themselves.

Melanie: What are some of the common diagnoses that you see in the clinic?

Dr. Druley: The most common one that we take care of is Beckwith-Wiedemann Syndrome or hemihypertrophy, so this is where children are born with part or all of half of their body can be enlarged and it can increase the risk of liver or kidney cancer. We have a lot of children on campus that have neurofibromatosis or similar syndromes. But the range of conditions that we are treating always grows so we probably have about 25 different diagnoses that we manage on a frequent basis.

Melanie: And tell us what does the current research look like? Give us a little bit of a blue print for future research in genetic predisposition for cancer in children.

Dr. Druley: Well, I think you know one of the biggest things is to really be able to predict who is at the most risk and who isn’t. Even though we say these children have an increased risk of cancer, you know the absolute risk is about five or ten percent, so you know, as many as nine or ten children that you see, out of ten or twenty are going to actually get a cancer. So, we treat them all the same. We screen them all the same because we don’t have a good understanding as to who is at most risk within that group, so the current testing is to try and further refine within known diagnoses which children are at the most risk for which types of cancer, but then we are also trying to broaden our criteria for who is at risk and we have done a lot of research lately showing that there are certain birth defects that aren’t part of a medical syndrome but just random birth defects that increase the risk of children getting cancer and that is particularly true for children that are born with birth defects in their central nervous system, their brain, and their spinal cord. They are at significantly higher risk for developing brain tumors and spinal cord tumors than children without these birth defects. So, that’s a group that historically hasn’t been longitudinally watched for potential cancers, but we are trying to change that.

Melanie: In summary, Dr. Druley, tell other pediatricians what you would like them to know about cancer predisposition in children and when to refer to a specialist.

Dr. Druley: Absolutely, I think cancer predisposition in children – we are really on the tip of the iceberg. It is much more common than people realize. As many as one third of the children that are diagnosed with cancer can be found to have a predisposition. So, if there is any concern about a particular constellation of symptoms, or family history, other diagnoses within the family or that particular child you know we are really keen on providing consultation to see if there are any merits to screening for genetic predispositions to cancer and then following those children and their entire families for the long-term.

Melanie: And what can a pediatrician expect from your team after referral in so far as communication with the referring physician and your team approach?

Dr. Druley: I think we work very hard to provide direct feedback to the pediatrician because again, these aren’t just single disorders, there is oftentimes several different diagnoses involved. So, we work with neurologists, radiologists, gastroenterologists, geneticists, and so we summarize the information from all these different subspecialists and we provide a note and follow up documentation directly to the general pediatrician for each child that gets referred with a very precise set of recommendations on the longitudinal screening that this child or this family might need; whether that is best done by the general pediatrician or with us, it really doesn’t matter as long as the child is receiving the proper surveillance.

Melanie: Thank you so much for being with us today. A physician can refer a patient by calling Children’s Direct Physician Access line at 1-800-678-HELP. That’s 1-800-678-4357. You are listening to Radio Rounds with St. Louis children’s Hospital. For more information on resources available at St. Louis Children’s Hospital you can go to That’s This is Melanie Cole. Thanks so much for listening.