Subtypes and Prognostic Factors in Erdheim-Chester Disease

Meyer Children's Hospital IRCCS

Status: Enrolling

Conditions: Erdheim-Chester Disease

Treatments: Genetic: Investigation of BRAF mosaicism

Study type: Interventional

Funder types: Other

Identifiers

NCT06317246

ECDSUB

Details and patient eligibility

About

Erdheim-Chester Disease (ECD) is a rare form of histiocytosis characterized by the proliferation of blood cells, known as histiocytes, which infiltrate various organs and tissues, often causing irreversible damage. The causes of the pathology are still unknown. Although the disease typically affects adult individuals, cases of pediatric-onset ECD have been described. However, there is a lack of detailed information on the phenotypic characteristics of these patients, and reliable data on response to specific therapies and long-term outcomes are missing. Three patients referred to our reference center for Histiocytosis present a concomitant BRAF-mutated neoplasm. Such an association could be due to the presence of mosaicisms for the BRAF V600E mutation. Mosaicism is a biological event defined as the presence of more than one genetically dissimilar cell population in the same organism and is an increasingly studied field, both in normal and pathological conditions. If proven in ECD as well, this mechanism could contribute to providing answers to the still open questions regarding the development of this disease.

Enrollment: 70 estimated patients

Sex: All

Ages: 1 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Prevalent and incident patients (adults and pediatric), with histologically confirmed diagnosis of Erdheim-Chester Disease according to the latest diagnostic recommendations;
• Signing of informed consent for study participation.

Exclusion criteria

• Patients for whom clinical and imaging data are not available and for whom it is not possible to retrieve histological samples."

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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70 participants in 1 patient group

Investigation of BRAF mosaicism

Experimental group

Description:

The study of BRAF mosaicism will be conducted on biopsy samples from patients with ECD and other neoplasms co-occurring with the BRAFV600E mutation. The samples will be labeled with anti-Pu.1-Alexa Fluor 647 antibody (which binds to macrophages), then DNA will be extracted using FACS method and amplified using MDA (Qiagen Repli-G Single-Cell kit). Quality control will be performed using Quant-it (ThermoScientific) and Agilent 4200 TapeStation. Eligible samples will undergo digital droplet PCR (ddPCR) and sequencing. ddPCR probes for wild-type and mutant alleles will be used. Sequencing will be performed using Illumina HiSeq 2500 system

Treatment:

Genetic: Investigation of BRAF mosaicism