Identification of Familial Hodgkin Lymphoma Predisposing Genes Using Whole Genome Sequencing

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Hodgkin lymphoma (HL) is a B-cell malignancy with suspected genetic predisposition.
• Familial clustering suggests a genetic component, but causative genes remain largely unknown.

Purpose of the Study:

• To identify genetic variants predisposing to Hodgkin lymphoma in familial cases.
• To functionally validate candidate genes involved in HL pathogenesis.

Main Methods:

• Whole genome sequencing (WGS) was performed on three HL-prone families.
• Variants were prioritized using a custom pipeline (FCVPPv2) and pathway analysis.
• Functional studies were conducted on candidate variants, including a DICER1 variant.

Main Results:

• WGS identified numerous variants, reduced by pedigree filtering and gene panels.
• Pathway analysis implicated genes in B-cell activation and cancer networks.
• A heterozygous missense variant in the DICER1 tumor suppressor gene was identified and validated as a potential HL predisposition factor in one family.

Conclusions:

• The DICER1 variant represents a potential genetic factor contributing to Hodgkin lymphoma predisposition.
• Further research is needed to identify and validate causative genes in other HL-prone families.