Inherited Genetic Susceptibility in Langerhans Cell Histiocytosis (LCH)
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|ClinicalTrials.gov Identifier: NCT04100408|
Recruitment Status : Recruiting
First Posted : September 24, 2019
Last Update Posted : December 16, 2019
|Condition or disease||Intervention/treatment|
|Histiocytosis, Langerhans-Cell||Other: Biospecimen Collection Other: Laboratory Biomarker Analysis Other: Questionnaire Administration|
I. To comprehensively characterize germline variants in SMAD6 and their association with LCH.
II. To identify novel germline variants associated with LCH.
III.To determine the role of genetic ancestry on LCH-related somatic mutations.
I. To integrate clinical and epidemiologic questionnaire data with genetic risk factor data from the Primary Aims to more comprehensively elucidate LCH susceptibility.
Case identification and recruitment followed by questionnaires and specimen processing.
|Study Type :||Observational|
|Estimated Enrollment :||647 participants|
|Official Title:||Inherited Genetic Susceptibility in Langerhans Cell Histiocytosis (LCH)|
|Actual Study Start Date :||August 30, 2019|
|Estimated Primary Completion Date :||September 30, 2024|
|Estimated Study Completion Date :||September 30, 2024|
Ancillary-Correlative (biospecimen collection)
LCH patients and their parents undergo collection of saliva or buccal mucosa samples for genetic mutational analysis. Germline DNA from saliva or buccal brushing will be sequenced, genotyped, and analyzed.
Other: Biospecimen Collection
Undergo saliva or buccal mucosa collection
Other: Laboratory Biomarker Analysis
Other: Questionnaire Administration
- Characterized germline variants in SMAD6 and their association with Langerhans Cell Histiocytosis (LCH) [ Time Frame: Up to 4 years ]Will re-sequence SMAD6 among LCH case-parent trios to characterize the association between SMAD6 inherited genetic effects and LCH susceptibility using targeted next-generation sequencing. We will also analyze de novo single-nucleotide variants (SNVs), copy-number variants (CNVs), and insertions/deletions(INDELs) obtained through SMAD6 sequence data generated from the biologic samples of the CCRN/PEC LCH case-parent trios.
- The frequency of de novo mutations and systematic assessment of the underlying genetic makeup of LCH [ Time Frame: Up to 4 years ]Will use the maximum number of LCH case-parent trios enrolled utilizing the CCRN/PEC with viable biologic samples to conduct genome-wide SNP genotyping. This methodology will identify new genes and pathways associated with LCH susceptibility. We will also determine the prevalence of novel de novo mutations associated with LCH in these case-parent trios. This will provide a systematic assessment of the underlying genetic makeup of LCH in a large sample of families.
- The difference in LCH-related somatic mutations by race/ethnicity due to underlying genetic ancestry [ Time Frame: Up to 4 years ]Genetic ancestry will be determined using germline genome-wide SNP array data generated from CCRN/PEC LCH cases in Aim 2. In parallel, we will determine patient somatic mutational profiles using a custom, targeted 91-gene panel. We will then conduct a genome-wide admixture-mapping scan to identify LCH-related loci that are associated with specific LCH somatic mutational profiles.
- The role of genetic ancestry on LCH-related somatic mutations [ Time Frame: Up to 4 years ]The analysis of data generated in this outcome measure will be primarily descriptive in nature. the objective will be to characterize LCH case-parent trios based on demographic, epidemiologic, and clinical characteristics. Findings from primary outcome measures findings will be validated and will assess if the frequency of validated inherited genetic variants differs by these characteristics.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04100408
|United States, Texas|
|Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Michael Scheurer, PhD 713-798-5547 Scheurer@bcm.edu|
|Principal Investigator:||Michael Scheurer, PhD||Children's Oncology Group|