Clinical trial NCT02193724: Feasibility of Generating Pluripotent Stem Cells From Patients With Familial Retinoblastoma
Official title: Feasibility, Validation and Differentiation of Induced Pluripotent Stem Cells Produced From Patients With Heritable Retinoblastoma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Retinoblastoma
Keywords: Heritable Retinoblastoma
Familial Retinoblastoma
Pluripotent Stem Cells
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: University of Wisconsin, Madison
First posted: 2014-07-18
Enrollment: 15
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will have a diagnosis of heritable retinoblastoma.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of samples which successfully produced iPSCs
timeFrame: Once at enrollment
Secondary outcomes:
measure: Number of samples with validated RB1-deficient iPSCs
timeFrame: Once at enrollment
measure: Number of samples that differentiate human iPSCs toward an eye field fate
timeFrame: Once at enrollment
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Rachel C. Brennan, MD
role: PRINCIPAL_INVESTIGATOR
References: