My patient doesn’t quite meet your study criteria, but I’m interested in having them enroll anyways. Is this possible?
Yes, we are happy to consider any patient for study participation. Please send the genetic counselor study coordinator a clinical summary along with a copy of the family history. Within a week you should receive a decision.

My patient meets your study criteria. Do I still have to send you the clinical and family history information before facilitating enrollment?
No. If a patient meets our study criteria you do not need to get approval from us beforehand.

My patient has already had clinical PTEN testing, can they still participate in this study?
Yes, especially if their results were positive or if a variant of uncertain significance was found. If results were negative, we’re happy to accept the patient if they meet our study criteria.

Can patients do clinical and research PTEN testing simultaneously?
Yes. The decision about what type of testing to pursue is up to the patient and their healthcare provider.

I’m not sure if my patient meets your criteria for MLPA testing, how can I find this out for sure?
First, see the eligibility criteria on the study website. If you still have questions, you are welcome to contact our genetic counselor study coordinator and she will be happy to tell you.

Does my patient need to have any other tests done before they can participate in your study?
No, but please use common sense. If a patient’s only features from the Clinical Features Checklist are breast cancer (diagnosed at 30), uterine fibroids, and has one lipoma, the patient qualifies for the study. However, it would be wise to check for BRCA1/2 mutations first, as the chance of finding a mutation in one of these genes is higher than finding a PTEN mutation. Using our grant funding as wisely as possible enables us to provide research participation to a great number of patients.

Why did you change your study requirements?
In order to obtain solid data that will one day be publishable, we need to have the ability to confirm the diagnoses being reported to us. We also need to know a head measurement, regardless of whether or not the patient is macrocephalic, to help us one day know the value of this variable in predicting whether or not a patient will have a PTEN mutation. If the requested documentation to confirm a diagnosis is not available to you to send to us, please ensure that the institution or facility where these records reside is listed on the patient’s medical release form so we can request them ourselves.

What’s the normal head circumference limit for adults?
Head size is not purported to grow after age 18, thus measurements at age 18 are utilized. Multiple growth charts have been published by various sources; our center is developing a study to hopefully answer the question “What is a normal adult head size?” Historically our group has used an upper limit of normal for men as approximately 58.0 cm and for women as approximately 57.3 cm. Please email pten@ccf.org if you’d like a copy of the chart found in SMITH’S Recognizable Patterns of Human Malformation published by Nellhaus, G. (Pediatrics, 1968; 41:106). For children age 3 years and younger, head circumference charts published by the NIH/CDC are available at http://www.cdc.gov/growthcharts/

40 mL of blood seems like a lot, especially for children. Can a patient send less blood for testing?
Yes, we understand that blood draws for children can be difficult! For children please try and obtain a minimum of 7 mL; we will try and work with whatever specimen we receive, but may request an additional sample if needed.

Do patients need to fast before having blood drawn for this study?
No.

Can I send you previously banked DNA or another tissue type for testing?
Yes. Although blood is our preferred specimen, we can also accept a minimum of 5 micrograms of previously extracted DNA. To discuss sending other tissue types, please email pten@ccf.org.

My institution does not use UPS – how can I go about sending samples to you?
Even if your institution does not contract with UPS, UPS can come and pick up packages from wherever you are if you call them directly at the number on the shipping label: 1-800-PICK-UPS. For international shipments we use DHL – please see our study website for special international shipping instructions. We do not use FedEx for cost considerations.

My patient got a bill for their research blood draw. Can they get reimbursed?
Yes. Please have the patient send their bill to Dawn Caraballo (address below). We cannot reimburse for blood draws done where venipuncture was done for clinical and research testing simultaneously.

Do DGGE and LightScanner have the same sensitivity as sequencing for detecting mutations?
For the PTEN coding region, our lab found that both DGGE and LightScanner picked up all the mutations detected by sequencing. Whenever an abnormality is noted, we do confirmation by sequencing.

Can your lab do clinical confirmation of patient results?
No. We are a research lab and are not CLIA-approved. CLIA-approved labs have strict quality control standards that research labs do not to prevent sample mix-up or mislabeling. Lack of regulatory oversight is one reason why it is not good practice to use research results for clinical management or to do clinical testing on a sample banked in a non-CLIA lab.

Why can’t you tell me my patient’s exact mutation result?
Our IRB prohibits us from doing so. They need to ensure that any research findings are confirmed in a clinical lab before being used for clinical purposes, such as management or predictive testing for relatives. However, we are able to release mutation nomenclature to the clinical lab of your choice for site-specific confirmation, which tends to be much cheaper than full gene analysis.

I used to be able to consent patients on my own – why did this change, and how can I become approved to do this again?
We undertook a review of our research charts and found some concerning patterns of error in the way consent documents were completed. To ensure the continued IRB approval of our study, a member of our research team needs to do consent for all patients at non-approved sites via telephone before their blood sample can be drawn.

My patient wants to participate in your study, but does not want to release any medical information to you. Can they still participate?
No. Research is a two-way street; we are happy to provide free PTEN research testing, but need clinical information to make progress with our research efforts and obtain grants to continue this study. A signed and completed medical release is required for participation. If required documents are not received in a timely manner, results will not be disclosed and the patient’s sample may be destroyed.

Patients used to be able to sign up for this study anonymously (without identifiers) – why was this option eliminated?
Very few participants selected this option, and on occasion it was selected in error, making patients wishing to receive results unable to do so. Again, clinical information is also required, and this information includes patient identifiers anyways.

My patient’s relative qualifies for your study. How can they sign up?
They would need to see if their current healthcare provider would be willing to facilitate their enrollment and complete all the required paperwork. Study enrollment is best facilitated by a genetics professional, but could be done by any healthcare provider willing to provide the required clinical information and take responsibility for receiving the patient’s results. Our genetic counselor study coordinator is happy to speak directly with any healthcare provider to guide them through this process.

What happens to the sample and paperwork after it arrives in your lab?
The blood sample is split up and given to lab members working on various DNA, RNA, and protein studies. Immortal cell lines are also created for future use. The paperwork is reviewed for completeness and clinical information is gathered and recorded in our database.

Will research team members ever contact my patient?
After the telephone consent has been completed, we would only need to contact the patient again if there is a problem with the consent document or sample that needs quick intervention. We will not contact patients directly about their results.

I have a general patient question or management questions about conditions in the PTEN spectrum. Can I call you for help?
Yes, we are happy to help answer these questions. Our genetic counselor study coordinator would be your best contact. If she cannot address the issue, she will consult with Dr. Eng or another specialist at the Cleveland Clinic who is part of our management team for persons with PTEN spectrum conditions.

Can patients come to the Cleveland Clinic for an appointment with Dr. Eng?
Yes. However, they should be aware that it would be considered a regular doctor’s office visit, and the patient and/or their insurance would be charged for the visit as well as the genetic counseling portion of the appointment. We cannot cover travel costs for clinic appointments. Patients wishing to schedule an appointment or discuss financial clearance can call our toll-free appointment line: (800) 998-4785, where they will speak with one of our patient service representatives.

How many samples does the study receive each month?
On average, 80-100 new samples are received each month for the PTEN study.

My patient wants their sample destroyed – how do I go about getting this done?
Please email Dawn Caraballo (carabad2@ccf.org) to receive a sample destruction form to have your patient complete and send back to us. Destroying the sample will ensure that no further research is done on stored materials or clinical information, but we cannot delete any results already gained from the patient’s participation. We are also required by the IRB to not destroy the paperwork and other information for destroyed samples, but this information will be kept separate from our other research files.

Are there other research studies available for people with PTEN alterations?
Yes; our group has developed two additional studies:

1. Identification of Neoplastic Risks in and Minimum Diagnostic Criteria for Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS) (CCF IRB#8510, P.I. Charis Eng, MD, PhD; also called “The Questionnaire Study”)

• Analyzes medical information obtained from questionnaires completed over a five-year period.
• Patients are eligible if they participate in our “Molecular Mechanisms Involved in Cancer Predisposition” protocol (CCF IRB# 8458, P.I. Charis Eng, MD, PhD) and are found to have a PTEN polymorphism, variant or mutation. The consent document for this study is sent to the referring provider with the confidential results e-mail for the patient to review.
• Dawn Caraballo provides informed consent and administers the questionnaires, usually by telephone. They are done yearly and typically take 20-35 minutes to complete.

2. An Examination of the Cognitive and Behavioral Characteristics Associated with Cowden Syndrome, BRRS, and other syndromes involving PTEN mutations. (CCF IRB# 7289, P.I.s Robin Busch, PhD and Charis Eng, MD, PhD; also called “The Neuropsychological Study”)

• Occurs on the Cleveland Clinic main campus; travel costs not currently reimbursed, but may be in the future.
• Participants must be at least 12 years old and test positive for a pathogenic PTEN alteration (i.e. not a variant or SNP)
• Patients undergo a day-long neuropsychological evaluation and a battery of tests to evaluate cognition, psychological function, and personality and will receive results.
• An informational letter about the study is sent to the referring healthcare provider with the patient’s results.

There are a few therapeutic clinical trials listed on www.clinicaltrials.gov that are studying the effects of particular targeted therapies for persons with PTEN mutations and tumors that have not responded to other treatments. Please see that website for further details; our genetic counselor study coordinator may also be able to provide you with helpful information about these studies.

For more info on the PTEN Questionnaire Study click here (PDF)

Current Research Study Contacts
General Research Line: (216) 445-7869

Genetic Counselor Study Coordinator: Jessica Mester, MS, CGC
Phone: (216) 636-5535
Email: pten@ccf.org

General Research Coordinator: Dawn Caraballo, BS
Phone: (216) 445-7869
Email: carabad2@ccf.org

Fax for both: (216) 636-0009 or (216) 445-6935
Address for both: 9500 Euclid Ave., NE50
Cleveland, OH 44195