Inherited Genetic Susceptibility in Langerhans Cell Histiocytosis (LCH)

Children's Oncology Group

Status: Active, not recruiting

Conditions: Histiocytosis, Langerhans-Cell

Treatments: Other: Questionnaire Administration; Other: Biospecimen Collection; Other: Laboratory Biomarker Analysis

Study type: Observational

Funder types: NETWORK; NIH

Identifiers

NCT04100408

AEPI17N1

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 647 estimated patients

Sex: All

Ages: Under 25 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• ≤ 25 years old at the time of original LCH diagnosis
• The patient must be enrolled on ACCRN07 and/or APEC14B1 and registered with COG by a North American member institution
• The patient must have a diagnosis of LCH (ICD Codes/Morphology: 9751/1; 9752/1; 9753/1; or 9754/3).
• The patient must be diagnosed with LCH on or after January 1, 2008.
• All questionnaire respondents must understand English or Spanish.
• All patients and/or their parents or legal guardians must provide informed consent.
• All institutional, FDA, and NCI requirements for human studies must be met.

Trial design

647 participants in 1 patient group

Ancillary-Correlative (biospecimen collection)

Description:

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.

Treatment:

Other: Laboratory Biomarker Analysis

Other: Biospecimen Collection

Other: Questionnaire Administration