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Genomic Medicine

Research

Home About Research Education Labs News Careers Contact

Our Laboratories

Genomic Medicine Institute laboratories are making discoveries in the areas of brain, cancer, heart, inflammation, systems biology, virology, and more.

Explore our Labs
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  • Research
  • Clinical Research
    Genetics of Pheochromocytoma & Paraganglioma About the PTEN Research Study: Molecular Mechanisms Involved in Cancer Predisposition Natural History Study of Individuals with Autism & Germline Heterozygous PTEN Mutations Predicting Efficacy & Safety of a SARS-CoV2 Vaccine in Patients with Cancer Predispositions (IRB 21-897) Closed Studies
  • Biorepository

Clinical Research

Clinical Research

Genetics of Pheochromocytoma & Paraganglioma

Eligibility Criteria

Patients may not self-enroll in this study; enrollment must be facilitated by a health care provider (genetic counselor, doctor, nurse, etc.).

Patients with the following will automatically qualify for study participation:

  • At least one pheochromocytoma or paraganglioma
  • Clinical or molecular exclusion of Multiple Endocrine Neoplasia type 2 and von Hippel-Lindau syndrome

We will also accept any patient with a known SDHB, SDHC, or SDHD gene mutation or variant of uncertain significance, even if they do not meet the above criteria.
If you have questions about eligibility, please email pgl@ccf.org or fax (216.636.0009 or 216.445.6798) the patient's pedigree and a clinical summary to the GC coordinator.

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 four items, please click here (PDF).

  • Permission to contact form (must be signed by patient)
  • CCF release form (must be signed by patient)
  • Banking checklist
  • Clinical features checklist
  • Pedigree
  • Medical records (Pathology report, imaging reports, metanephrine/catecholamines, genetic test results)

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 pgl@ccf.org.

Study Description/Methodology

Brief Description of Study
We are enrolling patients with pheochromocytoma and paraganglioma to study succinate dehydrogenase genes SDHB, SDHC, and SDHD. MEN 2A and VHL must be ruled-out through molecular testing or clinical assessment. We are also interested in enrolling patients who have a known SDHB, SDHC, or SDHD mutation even if they have not developed pheochromocytoma or paraganglioma. Mutation and deletion analyses are performed on the SDHB, SDHC, and SDHD genes.

Methodology
All samples undergo mutation scanning of the coding regions and exon/intron boundaries and MLPA of each exon of the succinate dehydrogenase genes: SDHB, SDHC, and SDHD. When an abnormality is noted on mutation scanning, sequencing of the section in question is performed to determine the exact nature of the abnormality. MLPA abnormalities are confirmed via quantitative PCR. Turn-around time for mutation scanning averages 3-6 months, but may be longer dependent on lab workload. We are currently unable to estimate the turn-around time for MLPA results, but hope to have these results available within 12 months after the release of the mutation scanning results.

Results

Clinically relevant results are provided via confidential email to the referring healthcare provider. Per our institutional IRB requirements, the exact nomenclature cannot be disclosed. However, if a deleterious mutation is identified, we can share the exact mutation nomenclature with the clinical lab of your choice for site-specific analysis. At present site-specific MLPA analysis is not clinically available, but we are happy to share abnormal MLPA results with the clinical lab of your choice as well.

Required Documents

This downloads page has been updated with new forms which will be effective from September 23, 2022 until September 22, 2023. We will not accept any previous versions of these documents. To access the new forms, please clear your browsing history and computer cache.

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

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


About the PTEN Research Study: Molecular Mechanisms Involved in Cancer Predisposition

The aim of this study is to learn more about susceptibility to cancer. The goal is to characterize the genetic changes that may increase an individual’s chances of developing cancer. The researchers are also looking to understand the relationship between microbes, cancer and autism spectrum disorder.

For Patients

For more information about this research study, view a summary (PDF).

If you have any questions about this study, please contact the PTEN clinical research team at 216.445.5850 or pten@ccf.org. You will be contacted by a member of the research staff who can explain what is involved with study participation as well as the informed consent and appointment scheduling process. 

For Providers
Eligibility

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 (PDF)
  • Adult patients with a score of 10 or greater per the Cleveland Clinic PTEN Risk Calculator
    Calculate Risk

  • 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 email pten@ccf.org or fax (216.636.0009) the patient's pedigree and a clinical summary to our study staff.

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)
  • Cleveland Clinic release form (must be signed by patient)
  • Banking checklist
  • Clinical features checklist
  • Pedigree template
  • Requested medical records (see Clinical Features Checklist [PDF])

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.

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.

Methodology
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
  • 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.

Results

Patient results are provided via confidential email 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

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 review the "The PTEN Study: Information for Prospective Participants" flyer (PDF) we wrote especially for you.

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:

Patient support groups:
www.ptenworld.com
www.ptenlife.com
www.ptenfoundation.org
PTEN/Cowden Clinic, housed at Cleveland Clinic

Required Forms

The PTEN Study: Required Documents Download Page
This downloads page has been updated with new forms which will be effective from September 23,2022 until September 22, 2023. 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 (PDF)

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

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


Natural History Study of Individuals with Autism & Germline Heterozygous PTEN Mutations (IRB 15-174)

The purpose of this study is to learn more about the symptoms and characteristics of individuals with autism and PTEN mutations, with the goal of informing risk management guidelines. The researchers may also learn new things about the genetic, biochemical, cognitive and/or behavioral problems associated with autism and/or PTEN mutations that may help diagnosis and treatment of individuals in the future.

For Patients

For more information about this research study, please view a summary (PDF).
If you have any questions about this study, please contact the PTEN clinical research team at 216.445.5850 or pten@ccf.org. You will be contacted by a member of the research staff who can explain what is involved with study participation as well as the informed consent and appointment scheduling process. 

For Outside Providers

Outside providers may not directly enroll patients in this study. If you have a patient who is interested in participation, please ask them to contact the PTEN clinical research team at 216.445.5850 or pten@ccf.org.
A member of the research staff will get in touch to explain what is involved in study participation, how we conduct informed consent and the process for research appointment scheduling.


Predicting Efficacy and Safety of a SARS-CoV2 Vaccine in Patients with Cancer Predispositions (IRB 21-897)

The primary aim of this study is to test in vitro (ie, in patient cells in the lab “dish”) the safety and efficacy of current mRNA-based SARS-CoV-2 (COVID-19) vaccines in patients with heritable PTEN mutations. Charis Eng, MD, PhD, is the principal investigator.

As of December 2021, this study has been enrolling two groups of research participants:
1) patients with PTEN mutations and 2) healthy controls with no pathogenic PTEN mutations.

Eligibility

Patients with PTEN mutations are being enrolled from Cleveland Clinic’s PTEN Multidisciplinary Clinic in Cleveland, Ohio. Patients who fit the following criteria qualify for study participation:

  • Have a PTEN mutation
  • 18 years or older
  • Have not yet received a COVID-19 vaccine OR have received at least one dose of the COVID-19 vaccine
  • Have been without any COVID-19 symptoms for at least 3 weeks, if previously diagnosed
  • Absence of auto-immune disease, immune disease or immunosuppression due to organ transplant or cancer
  • Absence of current infections, such as flu, gastrointestinal infection, cold and/or allergy flares

Healthy controls must be registered patients at Cleveland Clinic* who can travel to the main campus in Cleveland, Ohio. Individuals who fit the following criteria quality for study participation:

  • Absence of a pathogenic PTEN mutation
  • 18 years or older
  • Have not yet received a COVID-19 vaccine OR have received at least one dose of the COVID-19 vaccine
  • Have been without any COVID-19 symptoms for at least 3 weeks, if previously diagnosed
  • Absence of auto-immune disease, immune disease or immunosuppression due to organ transplant or cancer
  • Absence of current infections, such as flu, gastrointestinal infection, cold and/or allergy

*Family members of PTEN Clinic patients may also enroll as healthy controls as long as they fit the healthy control criteria listed above.

Study Involvement

Eligible subjects who wish to participate in this study must sign the informed consent form and complete one visit to the R1 outpatient lab at Cleveland Clinic’s main campus for a blood draw.  
Approximately 20 milliliters of blood (1-2 tubes) will be taken, which will be delivered directly to Dr. Eng's lab. Participants will receive a $20 stipend after the blood draw is complete.

Results

No results will be reported back to participants.

If interested in enrolling, please contact Beth Crouser at 216-445-5850 or crouseb2@ccf.org.


Closed Studies

  • CCF PTEN Breast Cancer Study (FOR CLEVELAND CLINIC PATIENTS ONLY)
  • Unexplained Hamartomatous and/or Hyperplastic Polyposis Study (a.k.a. The Funny Polyp Study)
  • Familial Barrett Esophagous and Esophageal Adenocarcinoma

Biorepository

Biorepository

The GMB serves as the foundation for evidence-based research for the GMI, the Cleveland Clinic, and our collaborators. Our biorepository has received, catalogued, processed, and banked in excess of 235,000 specimens from more than 16,200 patients. These samples are of numerous tissue types from patients and their family members located all over the world. The GMB has managed specimens that have resulted in more than 300 original peer-reviewed articles and greater than $25 million total direct costs in extramural funding over the last 7 years.
Samples received by the GMB are processed into a wide range of biomaterials using standardized laboratory techniques and quality control practices. Our services include the isolation of DNA and RNA for genetic studies, isolation of plasma or extraction of protein for proteomic studies, creation of immortalized cell lines from blood lymphocytes for biochemical research, and more. All sample information is entered into a laboratory information management system database (BSI) for cataloguing, coding, and storage as well as integration of additional research data. The GMB works closely with investigators and is committed to meet their comprehensive study goals.

Services & Fees

The Genomic Medicine Biorepository offers the following services to the members of the Genomic Medicine Institute, our collaborators, and members of the Cleveland Clinic family. Those outside of the Cleveland Clinic who may be interested in our services are encouraged to contact us for information.

All projects are subject to review by the GMB and our staff is available for individual consultation and experimental design upon request.

DNA Isolation
(Blood, paraffin-embedded tissue, frozen tissue, cell lines, and others)
This is the mainstay of genomics research and is used for many different investigations.

RNA Isolation (from various sources)
(Blood, cell lines, and others)
This allows for expression research, and combined with rtPCR (cDNA) offers a starting point for micro-array studies.

Spectrofluorometric Quantification of DNA
This differs from spectrophotometric (NanoDrop) analysis in that it specifically quantifies double-stranded DNA and is highly sensitive for quantifying small amounts of DNA.

Normalization of DNA
Preparation of DNA normalized to a specific concentration and volume.

Lymphoblastoid Cell Line Initiation
Initiation of lymphoblastoid cell lines provides a perpetual source of high molecular weight genetic material as well as protein, and opens the door to in vitro studies that cannot be done with primary cells.

Plasma or Serum Processing
This is a low-cost sample that is banked as a by-product when blood is submitted. This has tremendous potential with the emergence of proteomics as a new and exciting research tool.

Urine Processing
This is a standard diagnostic resource. As well, it has significant research value.

Cell Line Revival, Backfreeze, & Transfer
This process allows us to distribute cell lines that have been placed in cryogenic suspension without depleting potentially irreplaceable resources.

Sample Storage
This service is reserved for samples prepared by the GMB. These annual fees will be prospectively assessed at the beginning of each calendar year.

Biomaterial Transfer (other than cell lines or)
This service provides the mechanism to get samples to the investigator. This fee covers the administrative costs associated with preparing and documenting sample transfers.

Shipping
We can directly ship your samples to any lab domestic or international, for further analysis after processing.

Database Integration (BSI)
This is critical in the management of a modern biorepository - not only for sample management, but also for large-scale investigations involving clinical and research data.

Please contact the GMB at GMB@ccf.org for specific pricing.

Methods & Procedures

The methods implemented have been developed using standard protocols in the individual fields and following International Society for Biological and Environmental Repositories (ISBER) best practices. All protocols are subject to rigorous validation testing and strict quality assurance standards. Click on any of the below links to download the protocol in PDF form.

  • Plasma Isolation
  • DNA Isolation
  • RNA Isolation
  • Lymphblastoid Cell Line Initiation
  • Protein Isolation from Viable Cells
  • Collection of Small Tissue Biopsies for Frozen Sectioning
  • Preparation of EBV for Lymphoblastoid Initation
  • Placing Viable Cells in Cryogenic Suspension
  • Spectrofluorometric Quantification of dsDNA
  • Care of Lymphoblastoid Cell Lines
Forms

Click on any of the below links to download the document in PDF form.

  • Service Request
  • Transfer Request Form
  • Material Transfer Agreement – Incoming
  • Material Transfer Agreement – Outgoing
  • Shipping Form – Domestic
Facilities

The Genomic Medicine Biorepository is located in the Genomic Medicine Institute in the Center for Genomics Research, the latest addition to the Lerner Research Institute at The Cleveland Clinic. To ensure long-term reliability, samples received or processed by the GMB are stored in research-grade freezers and immortalized cell lines are indefinitely preserved in cryogenic suspension. All storage equipment is kept fail-safe through electrical backup circuits, alarm systems and temperature monitors.

Contact

For information regarding the services and operation of the Genomic Medicine Biorepository, please contact us:

  • GMB Lab
  • (216) 444-4731
  • GMB@ccf.org

Genomic Medicine Biorepository
Genomic Medicine Institute
Lerner Research Institute / R4
The Cleveland Clinic
9500 Euclid Avenue
Cleveland, Ohio 44195
Fax: (216) 636-0009

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