RETCELL: A Study of Children with Heritable Retinoblastoma

Feasibility, Validation and Differentiation of Induced Pluripotent Stem Cells Produced from Patients with Heritable Retinoblastoma

Category:

Solid Tumor

Diseases Treated:

Retinoblastoma (non-therapeutic)

Eligibility Overview:

Family history of retinoblastoma with one of the following:

  • RB1 mutation OR
  • Diagnosis of bilateral retinoblastoma OR
  • Diagnosis of unilateral retinoblastoma with RB1 mutation or MYCN amplification
  1. Brief Summary

    Retinoblastoma presents in a heritable or sporadic form and is fatal if left untreated. Despite years of study, the retinoblastoma cell of origin remains unknown. Researchers’ understanding of retinoblastoma tumorigenesis is limited by the rarity of retinoblastoma cases and tumor tissue available for examination.

    The field of stem cell research may offer an alternative path for investigating the developmental processes leading to retinoblastoma tumor formation. Human induced pluripotent stem cells (iPSCs) provide a unique opportunity to study fundamental questions regarding human retinal development and follow the lineage-specific cell production in vivo. The retina is an optimal system to investigate iPSCs further, as markers to distinguish each stage of retinogenesis are well known.

    In this study, researchers will use skin and/or blood samples from children with heritable retinoblastoma to generate induced pluripotent stem cells that are deficient in the RB1 gene or are mycn driven. The goal of this study is to determine if human RB1-deficient iPSCs can produce retina, and, furthermore, can give rise to retinoblastoma in culture. This unique opportunity to study the initiation of retinoblastoma in the developing retina will shed light on the cell of origin for retinoblastoma and enable analysis of the earliest molecular and cellular events in retinoblastoma tumorigenesis. 

    Primary Objectives

    • To establish the feasibility of producing induced pluripotent stem cells (iPSCs) from retinoblastoma patients with germline RB1 mutations (RB1-deficient iPSCs)
    • To validate human RB1-deficient iPSCs by confirming pluripotency and RB1 mutation
    • To differentiate the RB1-deficient iPSCs into retina as a model of the initiation of retinoblastoma in the developing retina

    Eligibility Criteria

    Inclusion criteria include:

    Family history of retinoblastoma with one of the following:

    • RB1  mutation OR
    • Diagnosis of bilateral retinoblastoma OR
    • Diagnosis of unilateral retinoblastoma with RB1 mutation or MYCN amplification

    Study Sites

    St. Jude Children’s Research Hospital
    Memphis, Tennessee

  2. About this study

    Retinoblastoma is an eye cancer of the retina, the thin membrane on the inside back of the eye. Retinoblastoma is often inherited, or passed down from parent to child. This is known as heritable retinoblastoma. Heritable retinoblastoma occurs when there is a change, called a mutation, in the body’s RB1 gene.

    Researchers in this study want to find out more about retinoblastoma and how it develops. To do that, they will collect skin OR blood samples from children with a family history of retinoblastoma. These cells will be used to grow special stem cells, also known as iPSCs (induced pluripotent stem cells), that also have the RB1 mutation. Researchers will study these stem cells to see how they operate and how they might develop into retinoblastoma.

    Purpose of this clinical trial

    The main purpose of the trial is to learn more about retinoblastoma and how it develops.

    Eligibility overview

    Family history of retinoblastoma with one of the following:

    • RB1  mutation OR
    • Diagnosis of bilateral retinoblastoma OR
    • Diagnosis of unilateral retinoblastoma with RB1 mutation or MYCN amplification
  3. RETCELL Quick View
    Sponsors St. Jude Children's Research Hospital
    ClinicalTrials.gov identifier NCT02193724
    Trial start date October 2014
    Estimated enrollment 20
    Study type Observational
    Conditions Retinoblastoma
    Ages All ages
    Principal investigator Rachel Brennan, MD
    Study Sites St. Jude Children’s Research Hospital
    For a consultation or to discuss RETCELL St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

Rachel Brennan, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.