Somatic Mosaicism in Twins Discordant for Childhood Cancer

Somatic Mosaicism in Twins Discordant for Childhood Cancer: a Pilot Study

Somatic mosaicism in cancer associated genes is one potential explanation for discordance in childhood cancer that has not been fully explored to date. This pilot study will focus on twins with central nervous system (CNS) tumors who are identified through the Children's Oncology Group's Project: EveryChild (PEC) registry or volunteer.

Study Overview

• Status: Recruiting
• Conditions: Central Nervous System Tumor; Somatic Mutation; Pediatric Central Nervous System Tumor; Discordant Twin
• Intervention / Treatment: Other: Biospecimen collection; Other: Questionnaire Administration

Detailed Description

PRIMARY OBJECTIVES:

I. To conduct a descriptive study of same sex twins (MZ and DZ) discordant for childhood CNS tumors identified through the Children's Oncology Group Project:EveryChild registry.

II. To compare the prevalence of somatic mosaicism in classic cancer-associated genes in monozygotic (MZ) twins discordant for childhood brain tumors. In our pilot study, we will sequence blood and saliva DNA samples from 25 MZ twin pairs using a panel of 94 known cancer associated genes.

SECONDARY OBJECTIVES:

I. To compare the profile of mutations detected in DNA extracted from pre- and post-treatment blood samples from a subset of CNS tumor patients. The purpose of this aim is to ensure that differences in somatic mosaicism detected in twin pairs are not caused by cancer therapy.

Outline:

Twins with CNS tumors will undergo blood and saliva DNA samples with the goal is to learn more about genetic differences that may lead to CNS tumor development.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Jenny Poynter, PhD; Phone Number: (612) 625-4232; Email: poynt006@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Contact: Jenny Poynter, PhD; Phone Number: 612-625-4232; Email: poynt006@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Newly diagnosed same sex twins with pediatric central nervous system (CNS) tumors

Description

Inclusion Criteria:

• Newly diagnosed patient with CNS tumor or have recurrent disease and enrolled on APEC14B1.
• Patient must have same sex twin. Note: (history of) treatment on a COG therapeutic trial is not required.
• Patients must be diagnosed at < 19 years of age at the time of diagnosis.
• A family is eligible to participate if the twin with the CNS tumor is deceased but has a blood sample banked through APEC14B1.
• All patients and/or their parents or legal guardians must provide informed consent. Assent will be obtained for participants between the ages of 8-17 years.
• All institutional, FDA, and NCI requirements for human studies must be met.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ancillary-Correlative; Twins with CNS tumors, identified through the Children's Oncology Group's Project:EveryChild (PEC) registry, will have both blood and saliva samples collected at the time of study enrollment.	Other: Biospecimen collection; Collection of both blood and saliva samples from participants at the time of study enrollment; Other: Questionnaire Administration; The brief questionnaire will assess health history, demographics, environmental exposures, family history of cancer, and birth characteristics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the prevalence of somatic mosaicism in classic cancer-associated genes in monozygotic (MZ) twins discordant for childhood brain tumors.	Sequence blood and saliva DNA samples from 25 MZ twin pairs using a panel of 94 known cancer associated genes.	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the profile of mutations detected in DNA extracted from pre- and post-treatment blood samples from a subset of CNS tumor patients.	Determine the frequency of somatic mosaicism in twins discordant for CNS tumors. Will use an exact test of proportions to determine whether the affected twin is more likely to have a mosaic mutation. The comparison of pre-treatment and post-treatment samples in the CNS tumor cases will include a descriptive comparison of the mutations identified in each sample	Up to 18 months

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jenny Poynter, PhD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: September 19, 2023
• First Submitted That Met QC Criteria: September 19, 2023
• First Posted (Actual): September 26, 2023

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: AEPI22N2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No