Feasibility of Generating Pluripotent Stem Cells From Patients With Familial Retinoblastoma

Completed

• Conditions: Retinoblastoma
• Interventions: Other: Skin Biopsy; Other: Blood Draw

• Registration Number: NCT02193724
• Lead Sponsor: St. Jude Children's Research Hospital

Brief Summary

The goal of this study is to determine if human RB1-deficient induced pluripotent stem cells (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 allow the investigators to study the earliest molecular and cellular events in retinoblastoma tumorigenesis.

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 karyotype, pluripotency and RB1 mutation.

* To differentiate the RB1-deficient iPSCs into retina as a model of the initiation of retinoblastoma in the developing retina.

Detailed Description

This is an observational study where a small skin cell sample or peripheral blood sample will be used to produce iPSCs. After RB1-deficient iPSCs are produced, their karyotype and RB1 mutation will be confirmed and their pluripotency will be tested by studying the expression of pluripotent genes and proteins according to standardized guidelines established for human iPSCs. After validation of the RB1-deficient iPSCs, they will be differentiated in the laboratory into retina following established protocols.

Study Timeline

• Study First Submitted: 2014-07-16
• Study First Submitted QC: 2014-07-16
• Study First Posted: 2014-07-18
• Study Start: 2014-11-04
• Primary Completion: 2019-08-23
• Study Completion: 2019-08-23
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-21
• Last Update Posted: 2020-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Research participant with heritable retinoblastoma and one of the following criteria:

  • Family history with RB1 mutation identified
  • Diagnosis of bilateral retinoblastoma
  • Diagnosis of unilateral retinoblastoma with RB1 mutation or MYCN amplification identified

• Participant or legal guardian/representative is able and willing to provide written informed consent.

Exclusion Criteria

• Participants who do not meet the inclusion criteria will be excluded.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Retinoblastoma	Blood Draw	Participants identified with heritable retinoblastoma will undergo a skin biopsy or blood draw to collect cells for processing and analysis.
Retinoblastoma	Skin Biopsy	Participants identified with heritable retinoblastoma will undergo a skin biopsy or blood draw to collect cells for processing and analysis.

Primary Outcome Measures

Name	Time	Method
Number of samples which successfully produced iPSCs	Once at enrollment	Skin biopsy or peripheral blood mononuclear cells will be collected from eligible, consenting participants and shipped directly to the University of Wisconsin for processing. All samples will be returned to the St. Jude investigator within two months of reprogramming for further analysis.

Secondary Outcome Measures

Name	Time	Method
Number of samples that differentiate human iPSCs toward an eye field fate	Once at enrollment	The best available methodology will be utilized for analyses of the RB1-deficient iPSCs.
Number of samples with validated RB1-deficient iPSCs	Once at enrollment	Samples will be analyzed for standard G band karyotype and FISH analysis (RB1 probe), targeted RB1 mutation (based on known mutation of patient from whom the sample was derived), and validation of pluripotency based on standard protocols.

Trial Locations

Locations (1)

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States