International Patient Meeting Report - 2012, Washington DC, USA
A Gastro-Intestinal Stromal Tumour is rare, but you are not alone!
Report from the 9th Paediatric & Wild-type clinic, National Institute of Health, Washington DC
Kindly prepared by Becky Bensenhaver who attended the clinic.
The Consortium for Pediatric and Wildtype GIST Research, coordinated by Dr. Lee Helman at the National Institute of Health, convened in Bethesda Maryland on June 13. The Clinic is a collaborative effort between clinicians and researchers to collect data as well as to investigate and develop treatment for Gastrointestinal Stromal Tumor (GIST) patients who do not have either c-KIT or Platelet-Derived Growth Factor Receptor alpha (PDGRFa) mutations. 85% of children with GIST, and 10 - 15% of adults with GIST do not have a mutation of either the KIT or PDGFRa genes. These patients are referred to as being Wildtype. The Clinic was started 4 years ago and much has been learned during this period of time.
What they've learned so far:
What they know about Pediatric GIST is that generally they are succinate dehydrogenase deficient, they are multifocal (meaning they are often in several places at once), they tend to be in the stomach, and they don't have mutations in kinase genes.
Following discussion of the plans for upcoming treatment options, Dr. Helman explained that now, for the first time, they plan to have Pediatric and Wildtype GIST treatments. This means that they will be transitioning from having the Clinic every 6 months to having the Clinic once a year. They are hoping many of the patients will be receiving treatments through participation in the studies and will be seen at the various institutions for ongoing follow up. Once a year NIH plans to convene those that need to be seen. The Consortium doctors would also meet once a year to discuss and coordinate research and treatment.
What they've learned about the genetics is that the overwhelming majority of what we now have more carefully defined as SDH-deficient (or multi-focal gastric tumors) lack succinate dehydrogenase immuno-reactivity, and of those that have this characteristic, over 90% express the insulin-growth factor 1 receptor (IGF-1R). Interestingly, something they didn't know until recently was that with most of the tumors that are SDH-mutant, the SDH mutation is in the germline, that is - not just in the tumor, but it is in every cell of the body. What this means is that every cell has one normal copy and one mutant copy of the gene, and what happens in the tumor is that you lose that normal copy which somehow leads to development of the tumor. They still are not sure what percent of the SDH-mutant tumors are germline, but they know that the percentage is high. This has ramifications for genetic counseling and other issues for how Pediatric GIST is managed. For example, it would affect how you screen, and how you would look for other diseases in the future. Until they have effective screening they aren't sure what to do with this information. Their recommendation, for families that want to look into this further, is for these families to have carefully certified testing performed upon their own initiation. They acknowledge that there are legitimate reasons either way for saying yes or no to further familial testing. Evaluation of data collected from the first 90 Pediatric and Wildtype GIST Clinic patients has been performed under research conditions. In order for Clinic participants to gain access to some of this information, they would have to perform a more rigid test to confirm it. This is information they had no idea about 4 years ago when the Clinic began. Moving forward, they are trying to work in unison with families to learn the best way to handle this information together. The work that the PAWS-GIST clinic will do will complement this.
Another interesting thing about these particular tumors is that they are "quiet" genetically. That is, many other cancers and tumors have many different chromosomes that get alterations. That is the case in KIT-mutant GIST. If you look at the chromosomes there are a number of alterations involved with most types of cancer. In the Pediatric GIST tumors, the number of alteration seen appears to be relatively small. They think one of the reasons they don't see many chromosomal changes is that Pediatric and Wildtype GIST may instead correlate very strongly with a change in what is called the epigenetic environment. In epigenetics, the gene itself is not changed, but the way the gene is packaged, called methylation, the way the chromosomes are put together, is altered in a way that is not yet fully understood. It is known that a change in the epigenetic environment affects which genes are expressed during a process called methylation. Methylation is not a genetic change, so it is not an inherited change, but it seems to change the way the chromosomes look to the body.
Tumor cells in KIT-mutant or PDGFRa-mutant GIST may look similar to SDH-mutant GIST under a microscope, but the latter stain differently because these tumors do not express the protein called succinate dehydrogenase, which results in hyper-methylation of the gene. These tumors look much different than the normal KIT-mutant GIST under immuno-histochemical staining. They are trying to use this information to develop therapies. They know about the IGFR over-expression and that is one potential therapy. One other thing that they have also learned about succinate dehydrogenase-deficiency is that it changes another enzyme that they think has to do with blood vessel growth . That is one of the reasons they are hoping that Vandetanib may be another treatment approach.
So just a quick word on treatment approaches:
Most of these tumors have what is called indolent growth, which is a good thing because it means that they grow very slowly. Now they don't have good treatments for them, which means they are very reliant on surgeons to resect them. Even when it gets resected at times it comes back, and sometimes they resect it again. Some patients can go years and years. So it doesn't grow rapidly and one of the things they've learned is that because they are multi-focal , and because patients will often present with pain or bleeding, rather than try to take out every tumor (sometimes to do that you would have to take out more of the stomach and you may create more symptoms than you would have by the disease itself). So, what they have learned is that the surgeons who treat this disease try to treat the symptoms (the pain, obstruction or bleeding) and not try to take out every last part of the tumor because we know patients can live for years and with this slow-growing tumor.
There is a report that states that some of the Wildtype GIST tumors respond to the kinase inhibitor drugs. Dr. Helman's opinion is that with SDH-deficient GISTS you will hardly ever see the tumors shrink in response to the kinase inhibitors. At best, these kinase inhibitors can make the tumor stop growing, which turns it into an indolent process again, and that is good. There is still debate about this. He expressed the hope that the upcoming Sutent dosing study being performed by Dr. Janeway can help determine what is the percentage of actual tumor shrinkage.
Future plans are to continue to have the NIH Pediatric and Wildtype GIST Clinic once rather than twice a year. At this annual Clinic meeting , specialists from multiple institutions and advocates can attend. They are hoping that the treatment studies will be accessible to everyone that has an interest in trying a new therapy. Hopefully, we will all learn together. As they identify some of the other genes that may be involved, maybe they can then have other therapies as well. So this is the beginning.
There are presently 3 clinical trials in development for Wildtype GIST
The first is a study being run by Dr. Margaret Von Mehren from Fox Chase Cancer Center through the Sarcoma Research Consortium (SARC). This trial will utilize OSI-906, an insulin-like growth factor inhibitor. It has been found that Insulin-like Growth Factor Receptor 1 (IGF-1R) is highly expressed in Pediatric GIST tumors in distinction to KIT-mutant GISTS that are susceptible to Gleevec. This trial is in the final stage of development. Dr. Von Mehren hopes that this trial will be open for accrual at multiple clinical institutions around the country in 3 or 4 weeks.
The second study presented is hoped to be open in approximately 2 to 3 months. This trial will utilize a drug called Vandetanib. The treatment rationale for Vandetanib, an inhibitor of vascular-endothelial growth factor (VEGF) and endothelial growth factor receptor (EGFR), is based on some information we have learned about the epigenetic alterations and about some related tumors that have similar mutations in succinate dehydrogenase. They've seen some responses in kidney cancers with these mutations to Vandetanib. It is thought that it's success can be attributed to the inhibition of vascular endothelial growth factor receptor (which inhibits the ability of the tumor to get oxygen through blood vessels). This drug has never been tried in GIST. It has been used in other pediatric tumors and other endocrine tumors, so this is a study that will open initially in just one location, at NIH in Bethesda. If it shows promise they will try to get the trial open in as many locations as possible.
The third study opening for Pediatric GIST is related specifically with the drug Sutent. This study to help to understand how to give Sutent to younger people who have GIST and to better understand how well it works.
Although Sutent has been used to treat GIST patients, neither OSI-906 nor Vandetanib have been used in GIST, so they have no reason to believe that one is going to work better than the other. Of course, if they did, they would put them in some kind of a priority. There is no reason if you decide to go on one and that you do well and then progress, that you couldn't then switch over to the other. So, if you start on one, it doesn't mean that you are limiting your options. You would have all of those options open in any sequence.
At the beginning of the third day of the 9th Pediatric and Wildtype GIST Clinic at NIH Dr. Fernanda Arnaldez met with the patients.
Dr. Arnaldez gave an excellent educational overview of topics. She then graciously and patiently answered the questions posed to her. Topics included in the session were such things as: the history of GIST, the distinction between KIT-mutated and Wildtype GIST, recent discoveries in the treatment of Wildtype GIST, discussion of upcoming clinical trials, etc.
What follows is Rebecca's summary of Dr. Arnaldez' discussion with the Clinic patients.
Gastrointestinal Stromal Tumors are a fairly new entity for patients and for the medical community. These tumors are some of the most common tumors of the upper intestinal tract such as the stomach and deodenum. The working hypothesis is that the tumor cells originate from the Interstitial Cells of Cajal. In the digestive tract pipeline you have muscles, but there are cells in between the muscle that are the pacemakers that allow the muscles to contract in an efficient fashion. These cells were named after the Spanish investigator Cajal who developed the techniques for staining them. Initially, they didn't have any molecular understanding of them. Some were called leiomyomas, some were called leimyosarcomas, some were called many other things. There came a point when they realized that there was a distinct entity called GIST. Many years ago the only way they had to categorize a tumor was to see how it looked under the microscope, that is all that you could go by. With the advances in technology, it became evident that certain genes are clearly mutated in the vast majority of cases of GIST.
What is a gene? In all cells of the body there is DNA. DNA contains all the information that tells us who we are and what our cells do. For simple illustrative purposes, DNA can be described as being a "street". Not very localized. But the DNA is packed in chromosomes, which would be like a "neighborhood". And within those chromosomes there are little pieces, each of them that have all the information that is needed to perform one function. That would be like a "block" of streets that give a more specific address. What genes really do is to tell the cell how to make proteins, and proteins are the things that make the cells work and tell the cells what to do.
In regard to GIST, the first mutations that were discovered were in KIT and PDGFRa. PDGFRa stands for the receptor for the growth factor that was initially described as being derived from platelets, but then it was discovered that it was involved in many other things. Early on, it was thought that all GISTS were KIT or PDGFRa mutated, but it turned out that this is not true. Initially, for the vast majority of adults that have KIT or PDGFRa-mutated GIST, therapy equalled surgery. Recurrence equalled surgery. Further recurrence equalled surgery. There was nothing else to do. Everything changed when we began to develop a better understanding of which gene was affected, which protein that gene making (or making the cell make), and how we could create molecules/medicines/treatments that could modify what that protein is doing. For example, if that protein is acting up too much, to inhibit it. If that protein is acting up too little, to stimulate it. If it is behaving wrong, just block it. This is a work in progress that is happening in all cancer research.
Imatinib (Gleevec) initially was a drug created for a particular kind of leukemia. It was not only a revolution for leukemia, it was a revolution for all molecular biology in cancer treatment. For the first time ever there was a drug that was designed specifically to block a protein that they knew was working wrong in a cell. This started the era of targeted therapies. Targeted therapy does not just use toxics, but rather uses a biologically designed agent that is going to target specifically what is wrong with a cancer cell. It sounds like a beautiful story, but here is still a long way to go and it is not as perfect as it was expected to be at the outset.
When it was discovered that KIT and PDGFRa are overactive and mutated in conventional GIST, two and two were put together, it was figured out that imatinib blocked not only the abnormal leukemia proteins (called the BCR-ABL fusion gene) but also inhibited KIT and PDGFRa. This revolutionized the treatment of adult conventional KIT-mutated GIST. It gave GIST patients with this mutation much hope.This really changed the way GIST was treated for 85% of the patients.
So what happens with the remaining 15% of the patients? Approximately 5 or 6 years ago, during an ASCO meeting, Dr. Helman was speaking with Dr. Pappo. They wondered "how can it be possible that while there were many advances being made in the treatment of GIST, there was a population of GIST patients who did not have the mutation, a population of patients for which they had no treatment at all? And worse, they know nothing about their biology". Basically, you can't treat what you don't know. You need to know who the enemy is. Knowing the biology is the first step towards finding medicines that work. So, the first step was to investigate the biology in order to be able to design therapies. That's how the GIST Clinic was started. A lot of the credit for this has to go to a Post-Doctorate Fellow in Dr. Helman's lab who has now left the NIH, whose name is Su Young Kim. A wonderful physician and a wonderful person. He was the executive arm of Dr. Helman, pulling all of this work together. With the start of the Clinic, the doctors had the privilege of meeting the patients. They are very thankful to all of the present patients, to all of their predecessors, and those who will come in the future. There is no way they could have found out as much as they have without the patients' involvement and willingness to attend the Clinic. As a result of the patient data collected, they have been able to begin to sequence genes that they believed could be responsible for Pediatric and WildtypeT GIST. To sequence a gene means to know exactly what the DNA in that gene says. Once that they had references regarding what should be the "right way to say it", they could begin to detect spelling errors in the gene and begin to suspect that that these errors were mutations. They then began to wonder whether the protein that is produced by this mutated gene may be causing the GIST?
Initially, when the scientists looked at the vast majority of the tumors of the patients who came to the Clinic under a microscope, they were only able to see that they knew to look for. They looked at characteristics of the cells, such as the shape, stained it with conventional methods, look under the microscope again, and made a description. But, you have to know that you are looking for a particular protein to know to apply a particular stain that is going to stain it differently because otherwise you miss information. So when they started to look for SDHB staining, based on some of the sequencing results and some of the other biology behind it, it became really clear: many of the tumor samples of KIT-mutated GIST would have a totally normal stain for SDHB. But when they looked at patients with Pediatric or WT GIST, that protein was gone.
What is SDH? This is going to be an oversimplification: When you eat food, food is broken down in your gastrointestinal tract and ultimately has to be broken down into pieces--molecules such as protein and lipids that go to the cells. The cells have to be able to process these pieces and to transform that into the energy that the cell can use. The process of transforming nutrients into energy involves very sophisticated cell machinery utilizing many different proteins. One of these proteins is SDH. Basically, SDH is a molecule. The SDH subunits such as a,b, c, and d assemble together to build the same complex like different bricks in the same wall. All of the subunits have to be healthy in order for the machinery to work well. In the end, we know that the SDH job function is to help the cells process nutrients in order to get energy for the cell's survival. Since this is a cycle, when this machine doesn't turn well, there is build-up of products that shouldn't be there. At this point, the hypothesis is, that a build up of some of these products can poison the anti-cancer regulating mechanisms.
We have learned that Wildtype GIST behaves differently from KIT-mutated GIST in that it is more common in females, it is located predominantly in the upper GI tract (ie the stomach and duodenum) rather than the lower GIST tract (ie the jejunum and the ileum). Wildtype GIST is most often SDH-deficient, which had led them to wonder "what is happening with the SDH gene"? They have been able to find mutations of the SDH gene in many of the patients. So, they went from saying "85% of the patients with GIST have KIT and PDGFRa mutations and yet some of them don't" to instead say "these patients who have these distinct kinds of tumors look this way under the microscope, have SDH-deficiency and many of them have SDH mutations". They believe that the mutations are related to the way the protein works, and they are suspicious there might be other mutations that they haven't yet been able to identify.
So, how can they use the new information to help design treatments? This is very complex process. The first thing you swear when you go to medical school is "Do no harm". So anytime you are making your best effort to help, you have to be extremely careful to make sure that even in perfectly good faith, you are not doing anything that is going to be detrimental. That is why the development of new drugs and new treatments, (without getting into the financial aspects, just talking about regulations) is such a lengthy process. First, you must have enough research evidence behind it. Secondly, patients should be protected.
So, where are they now in this process? They are in the process where some of the the Wildtype GIST findings can be translated safely into clinical trials.
The first trial is planned to be open in June at Fox Chase in Philadelphia under the direction of Dr. Margaret VonMehren through an institution that is called SARC (the Sarcoma Alliance for Research through Collaboration).
Here is the rationale for the trial: When you look under the microscope there are some distinct features of Pediatric and Wildtype GIST. One of the features is that there is increased expression of a protein called Insulin-Growth Factor 1, in the lingo IGF-1R. What is that? There are many growth factors, many substances that our body normally produce to keep us functioning and to keep our cells growing. IGF-1R is one of them. You can see by the name, that yes, it is similar to insulin in many ways, but is not exactly insulin. IGF-1R is involved in many things, including making us grow from when we are kids to when we are adults. This receptor is overexpressed in Wildtype GIST and in many other types of cancer. There is a new drug that blocks this receptor from working. This is the drug that Dr. VonMehren is going to be assessing in patients with GIST at Fox Chase
What does it mean when you say that a trial is "open"? Because the first consideration when trying a new drug in a new patient population is "Do no Harm", the first thing you ask is "is this drug going to cause any problems"? And the next one is "is this drug going to help". To define that really carefully you need to follow a protocol. A protocol directs what physicians and researchers are allowed and not allowed to do in order to protect our safety. The trial doctors write the protocols and they are reviewed by regulators. Once all of the pre-opening regulators parameters are met, the investigator, in this case Dr. Van Mehren, is allowed to start enrolling patients, allowed to start giving the drug to patients with GIST and monitoring their response, their tolerance, etc. How you get access to the trial is usually less cumbersome than you would think. One way is through a website calledclinicaltrials.gov, where clinical trials are listed. Another way is to send an email, or have your physician send an email, to Dr. Von Mehren asking if the trial is accepting patients.
The second clinical trial that is becoming available for Wildtype GIST patients is a study that will be run through the NIH in Bethesda utilizing a drug called Vandetanib. The rationale for this trial is based on the fact that mutated or deficient SDH is not able to participate in the process that transforms food to energy. This disruption causing intermediate products to build up, poisoning some of the mechanisms that control cancer growth. As this trial protocol is being developed, they are asking questions such as: "Is it safe? Does it make sense? How are we going to do it? How are we going to protect patient safety"? It is projected that the Vandetanib trial will be open for patient recruitment in about 3 or 4 months.
Question: Can you go over Carney Stratakis Syndrome?
Answer: When we started to see that in the SDH-deficient tumors the protein wasn't present, and that we had mutations in SDH in different subunits, we asked: "Is that happening in any other diseases that we know of?" The answer has been yes for many years. SDH mutations of different subunits, with different flavors, with different formats, have been known for a long time. One of these situations pertains to familial paragangliomas. This kind of paragangliomas can co-exist with GIST. So that was an investigational lead. Furthermore, you have all heard of Carney's triad-- where these two entities are associated with pulmonary chondromas, which are benign tumors of the lung. They are called chondromas because they are made of cartilage. The lung is like a sponge, but you also have your bronchioles that are made of cartilage. When the cartilage grows too much, without necessarily being malignant, it can make a lump of cartilage, and that is called a chondroma. Chondromas can be present for years without causing troble. It all depends where the chondroma is located.
Basically, those are our historical predecessors in terms of "Gee, what happens when this SDH family of proteins is not working well?, or "What other things can happen as the result of the presence of an SDH gene mutation.?
Question: Can SDH subunit a,b,c,and d all be germline mutations?
Answer: Regardless of the frequency with which you expect them in the population, when you find a sequence of DNA that is not what it should be there can be a mutation. There can be two different situations with these mutations. One, that you get a biopsy of the the tumor, you look at the tumor, and you only find the change or mutation there, in the tumor. But when you look at any other single cell in your body, it is not there. So you assume that something happened that caused the cell of origin of this tumor to have this mutation and to grow to develop into the tumor that is not present anywhere else. That is what we call a somatic mutation, something that is present only in the tumor. In contrast, there are germline mutations. Germline refers to the very line of the initial origin, mutations that were present sometimes at birth, sometimes at conception (that were present way before the tumor started and can oftentimes be inherited), Germline mutations are present in every single cell of your body. So those are descriptions of somatic vs. germline mutations. Now to make sure this is clear to all of you, having a germline mutation in any gene in general, doesn't mean that you are going to have problems such as we have been discussing. Usually, the accepted hypothesis for any kind of cancer or tumor development is that when you have a germline mutation, you need other things to happen on of that for the situation to end in a malignancy. Usually, it is not just having a germline mutation that is going to cause you to have problems. There are many things that have to happen in between.
Question: If researchers have GIST tumor sample and no blood sample can they determine if a mutation is somatic or germline? Do you you need both types of samples available?
Answer: Yes, you need both. Sometimes, there are tricks that geneticists use looking for particular sequences or sometimes a particular type of mutation has been described very classically in the liturature as being germline. So when you find it in the tumor and you don't have blood, you can assume that it this is a germline mutation. There are a lot of shades and colors to it, but the reality is, if you are going to be absolutely strict about determining whether a mutation is somatic or germline, you need a tumor cell sample as well as either blood or saliva.
Question: In the DNA of a germline mutation, you have two copies of an allele and you've lost one. In the tumor you lose the second allele and the tumor develops. So, when you have a somatic mutation (not germline) that occurs at the location of the tumor: does this mean that you have somehow you lost both copies of the allele?
Answer: Sometimes you have lost both, Sometimes you lost one and something happened to the other one to damage it or alter it's function. Sometimes you have one of the alleles that is not working well and this doesn't show up until you lose the other healthy allele that was doing all of the work.
Question: If slides are sent to a research facility: can the researchers stain an unstained slide to obtain more information, or do the need to have a paraffin block tumor in order to do that? You can't take the cover off of an unstained slide and stain it, can you?
Answer: That has been a great limitation for cancer research for many years. How to get information from a slide rather than getting everything from fresh tissue. It seems easier if you have just come out of surgery and you have the tissue right there. What happens when you have a block that has been archived for 10 years or an unstained slide? The technology to perform mutation testing on an unstained slide only recently came available. It is called laser capture microdissection. That means there is technology available now where you can use a very sophisticated microscope to point out a single cell or two on an unstained slide or a tissue block. You can isolate those cells, capture the DNA and the genetic material that is present within, taking that itty-bitty amount of genetic material to do mutational testing.
Question: Can you do the stain testing on these extremely small samples ?
Answer: You can, it sometimes works, it sometimes doesn't. The reason for this is that most of the stains are based in antibodies. If that protein is totally preserved in the tumor throughout the time is is archived in pathology, that can be detected. But sometimes is just doesn't work, but it is not for lack of effort.
Question: How do we find out the results of our SDH testing and blood work ?
Answer: You may need to undergo SDH testing at an independent lab. The SDH status findings obtained by the Clinic researchers are obtained under research conditions. There is a diference between a research test and a clinical test. A research test is not as rigorous as the clinical test performed in a CLIA certified lab. If you have questions regarding your SDH status, it is recommended that you work with a genetic counselor, such as Dr. Raygade who is associated with the Pediatric and Wildtype GIST Clinic.
Question: Can previous Clinic participants have access to the NIH genetic counselor to try to learn more about what mutations they may have.
Answer: Yes, previous participants can contact the Clinic genetic counselors for follow up.
We hope that this discussion is going to be very different two years from now, or three years from now.
NIH Clinic - June 13th 2012 - Questions posed to Dr. Helman:
Question: Has it been determined yet what the age limit will be for the participants in the Vandetanib trial?
Answered by Dr. Fernanda Arnaldez from NIH: Even though initially they were thinking they would limit the trial to Pediatric patients, after further discussion they decided that the adult WT population would also benefit, so they have decided to accept adult patients. They have not determined the actual age limit as of yet. Dr. Helman expressed his hope that the trial will be just limited to patients who are SDH-deficient. To him, the age is irrelevant. Dr. Von Mehren stated that the IGF-1R study at Fox Chase Cancer Center is going to be open to all patients who do not have KIT or PDGFRa mutations. During the course of the study they will be looking at patients for BRAF mutations and looking at the SDH status of patients. However, they had not planned on doing screening for SDH status up front. Dr. Helman stated that Dr. Miettinen, pathologist at NIH who has been studying GIST tumor samples for years, had recently shown data that the IGF-1R over-expression is almost, if not 100% exclusively the gastric GISTS. So I think we're talking about Wildtype non-KIT or PDGFRa-mutant gastic GISTS that would make up the vast majority of those that would go on that particular study. This would basically be similar to what the Vandetanib study would treat because I don't know that we've seen SDH-deficient tumors not in the stomach.
Question: What is the difference between an SDH-deficient and a germline mutation?
Dr. Helman: There appear to be a few cases where there seem to be SDH-deficiency and it may be what is called an acquired mutation only in the tumor and not in every cell in your body. The technical term for this is a "somatic mutation" (as opposed to a germ-line mutation). Dr. Janeway contributed, stating that there are probably some SDH-deficient tumors that don't have either somatic or germline mutations in any of the five different SDH genes that we know about, either in the tumor or in the all of the cells of the body. We don't know yet what the percentage of the patients fit into this category.
Question: "Why would someone not be interested to learn if they have an SDH mutation?"
Dr. Helman: "I'm sure all of you have heard some of the controversy in the newspapers in the last year on mammography screening for breast cancer and also PSA screening for prostate cancer. The reason it became controversial is: "Why would you screen for something that you can't do anything about". Dr. Helman's opinion is that the most important time to know is if you could change something with that knowledge. If you have knowledge you can't act on, it becomes somewhat of a personal choice. Some people think that the more knowledge you have, the better. Some people feel like sometimes you know too much, especially if you can't do anything about it.
Question: "Do parents get tested to see if we have this gene?"
Dr. Helman: That's another option, and that is something that we often talk about. If you had a child with a germline mutation, you may want to know - "did it come from my mother or did it come from my father?" Maybe that's important to know, maybe it's not. What they encourage is that you have these discussions with a genetic counselor because they are really the ones trained and equipped to go over all those issues. Of course, the Clinic staff are happy to talk to you as well, but genetic counselors are the specific professionals trained in this field. A comment was made by a Clinic Participant that the decision of whether or not to have genetic counseling could be a factor weighing on those trying to decide whether or not to have children.