An observational study in Histiocytosis, Langerhans-Cell, sponsored by Children's Oncology Group. Active, not recruiting at 1 site in United States. Open to participants aged Up to 25 Years. Per ClinicalTrials.gov, last updated 2026-01-09.
Sponsored by Children's Oncology Group · Observational
The long-term goal is to define the mechanisms of pathogenesis underlying Langerhans cell histiocytosis (LCH). The overall objectives of the current study are to characterize the role of SMAD6 inherited genetic variation on LCH susceptibility and identify germline genomic regions associated with LCH somatic mutations. Building from preliminary data, the central hypotheses are: (1) causal genetic variants in SMAD6 underlie susceptibility to LCH, and (2) differences in LCH-related somatic activating mutations by race/ethnicity are related to Amerindian (i.e., Native American) genetic ancestry. The Central hypothesis will be tested by pursuing the specific aims.
PRIMARY OBJECTIVES:
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.
EXPLORATORY OBJECTIVES:
I. To integrate clinical and epidemiologic questionnaire data with genetic risk factor data from the Primary Aims to more comprehensively elucidate LCH susceptibility.
OUTLINE:
Case identification and recruitment followed by questionnaires and specimen processing.
80 studies on the registry are indexed under Histiocytosis, Langerhans-Cell; 22 are open to participants now.
This study's planned enrollment of 647 is above the median of 97 across 14 observational studies indexed under Histiocytosis, Langerhans-Cell.
Browse Histiocytosis, Langerhans-Cell studies →Children's Oncology Group is the lead sponsor of 436 studies on the registry; 34 are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients diagnosed with Langerhans cell histiocytosis (LCH) on or after January 1, 2008.
Inclusion Criteria:
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 · Other: Laboratory Biomarker Analysis · Other: Questionnaire Administration
Undergo saliva or buccal mucosa collection
Correlative studies
Ancillary studies
Characterized germline variants in SMAD6 and their association with Langerhans Cell Histiocytosis (LCH)
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.
Time frame: Up to 4 years
The frequency of de novo mutations and systematic assessment of the underlying genetic makeup of LCH
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.
Time frame: Up to 4 years
The difference in LCH-related somatic mutations by race/ethnicity due to underlying genetic ancestry
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.
Time frame: Up to 4 years
The role of genetic ancestry on LCH-related somatic mutations
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.
Time frame: Up to 4 years
This study is active, not recruiting, as verified in Jan 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Histiocytosis, Langerhans-Cell→
Children's Oncology Group