Patients may not self-enroll in this study.
Enrollment must be facilitated by a health care provider (genetic counselor, doctor, nurse, etc.) able to take responsibility for receiving the patient's results:

Please be aware that an OFC (head circumference) measurement is a required data point for all study participants. You may not submit a patient for this study without this measurement. Please ensure that the measurement is documented in the patient's clinic notes for confirmation purposes.

Patients with the following will automatically qualify for study participation:

  • Two major, one major + 2 minor, or 3 minor criteria from our Clinical features checklist
  • Adult patients with a score of 10 or greater per the Cleveland Clinic PTEN Risk Calculator
  • Pediatric patients with macrocephaly plus at least one of the following:
    • Autism/mental retardation/developmental delay
    • Lipoma, biopsy-proven trichilemmomas, oral papilloma, or hemangioma
    • Arteriovenous malformation
    • One or more gastrointestinal polyps
  • Known PTEN mutation or variant of uncertain significance
  • Lhermitte-Duclos disease
  • Pigmented macules of the glans penis
  • Clinical diagnosis of Proteus or Proteus-like syndrome

If you have questions about eligibility, please e-mail or fax the patient's pedigree and a clinical summary to our study staff: pten@ccf.org / fax: 216-636-0009 .

Exclusion Criteria

Please do not submit the following:

  • Patients with non-PTEN genetic testing (i.e. BRCA1/2 testing) pending. For patients meeting our eligibility criteria, we are glad to enroll them in research regardless of clinical PTEN testing status; we just ask that a copy of the clinical testing results be sent to us when available.
  • Patients with other diagnostic testing that explains their qualifying features. Example: patient has endometrial cancer, fibrocystic breast disease, lipoma, and a deleterious MSh3 mutation; we would not "count" the endometrial cancer diagnosis towards study qualification.
  • While we do not strictly require that other diagnoses be ruled out prior to enrolling patients in this study, we do ask that you help us use our research funding as wisely as possible. For example, while a patient with breast cancer at age 30, lipomas, and uterine fibroids qualifies for our study, the patient's risk for BRCA1/2 mutation is likely greater than that for a PTEN mutation, and we would appreciate that diagnosis being ruled out first. Our genetic counselor coordinator is glad to discuss the differential diagnosis or testing strategy for any patient.

Enrollment: Non-IRB approved sites

This is the enrollment process for most providers. Informed consent must be performed by a member of our research staff before the patient's blood sample is obtained. After you recognize that the patient qualifies for our study, please complete the following and send to us by fax or postal mail. To download the first five items, please click here.

  • Permission to contact form (must be signed by patient)
  • CCF release form (must be signed by patient)
  • Banking checklist
  • Clinical features checklist
  • Pedigree Template
  • Requested medical records (see Clinical features checklist)

Please do not draw the patient's blood to send with these documents. After we have received these documents and verified that all information is complete, our staff will mail the patient a consent document and sample collection kit and contact the subject to consent them. We will email you after we have consented the patient to keep you updated on their involvement. Samples received before the informed consent process has been completed may be destroyed.

If you are interested in becoming an IRB-approved site, which would grant you the ability to complete the informed consent process for your patients, please email pten@ccf.org.

Enrollment: IRB approved sites

At present, the few institutions that have put our protocol through their institution's IRB may provide informed consent for patients at their facility. These sites have already received our informed consent document and may request additional copies by calling (216) 445-5850. If you are from an approved site, please click here for detailed instructions regarding the proper way to complete the informed consent document and other required study paperwork. Failure to complete this paperwork as described may result in the destruction of the patient's sample.

Study Description/Methodology

Study Description

This is a multi-faceted research study that combines clinical patient information with DNA, RNA, and protein studies of the PTEN gene and related pathways. We are studying the frequency of particular characteristics such as cancer diagnoses among those with PTEN alterations; working to clarify variants of uncertain significance; and exploring alternative mechanisms of disease in patients without identified mutations. We ultimately hope that this research will lead to the development of targeted molecular therapies for persons with PTEN alterations.


All samples undergo mutation scanning via LightScanner of the PTEN coding region, exon/intron boundaries, and flanking intronic sequences up to approximately +/-40 bases. When an abnormality is noted, sequencing of the section in question is performed. Each sample also undergoes sequencing of the core promoter region (approximately -1300 to -700). Turn-around time for this testing averages 3-6 months, but may be longer depending on lab workload.

MLPA (large rearrangement) analysis of all nine PTEN exons with confirmation by quantitative PCR will be done for the following patients:

  • Patients who meet the International Cowden Consortium’s criteria for the diagnosis of Cowden syndrome (version 2000, please click here to see these criteria.
  • Patients with a Bannayan-Riley-Ruvalcaba, Proteus, or Proteus-like syndrome phenotype
  • Adult patients with a score of 10 or greater per the Cleveland Clinic PTEN Risk Calculator

Please contact contact study staff (pten@ccf.org) for questions regarding MLPA eligibility. We are currently unable to estimate the turn-around time for MLPA results.


Patient results are provided via confidential e-mail to the referring healthcare provider. Per our institutional IRB requirements, the exact nomenclature cannot be disclosed. However, you will be informed if results were negative (no alteration identified) or if a deleterious mutation, single nucleotide polymorphism (SNP), or variant of uncertain significance (VUS) is identified. If a deleterious mutation is identified, we can share the exact mutation nomenclature with the clinical lab of your choice for site-specific mutation confirmation. At present site-specific MLPA analysis is not clinically available, but the clinical lab performing confirmatory studies may appreciate having this information for patients with large rearrangements detected with this technology.

Please be aware that we will not release the patient’s results to you until all required study documents have been completed and received.

Information for Current or Potential Participants

Information for Current or Potential Participants

Thank you for either being a part of or considering enrollment in our research. While we work to improve the content of this site, we hope you find the information below helpful.

Considering study participation?

Please click here to find a flyer we wrote especially for you, "The PTEN Study: Information for Prospective Participants"

Already enrolled?

Please check back for summaries of the research that your participation helped our laboratory accomplish.

Do you have a PTEN mutation?

Here are some resources you may find helpful:

PTEN/Cowden Clinic, housed at the Cleveland Clinic: http://my.clevelandclinic.org/genomics-genetics/subspecialties/pten-clinic.aspx

Required forms

The PTEN Study: Required Documents Download Page

This downloads page has been updated with new forms which will be effective from September 23,2021 until September 22, 2022. We will not accept any previous versions of these documents. To access the new forms, please clear your browsing history and computer cache.

Description of PTEN Study for potential participants

For non-approved outside sites to send to CCF to have a patient consented:
Enrollment Documents: Non-IRB Approved Pedigree Template (found with enrollment documents), and Requested medical records available to you.

For our Spanish speaking patients:
Permission to Contact (Spanish)
Medical Release Form (Spanish)

For IRB-approved outside sites: All required consenting documents will be sent to you individually by our research coordinator. Along with those documents, please complete and send the following:
Enrollment Documents: IRB Approved
Please also see the following:
Informed Consent Instructions
Specimen and Shipping Instructions