Familial hematological malignancies: ASXL1 gene investigation

Area of Science:

• Genetics
• Hematology
• Oncology

Background:

• Familial aggregation of hematological malignancies suggests a genetic predisposition.
• Few predisposing genes have been identified due to the rarity of familial cases.
• Previous studies identified PRF1 and CEBPA variants, prompting further investigation into cooperating genes.

Purpose of the Study:

• To investigate the potential involvement of the germline additional sex combs-like 1 (ASXL1) gene in familial hematological malignancies.
• To determine if ASXL1 mutations contribute to the genetic background of these diseases.

Main Methods:

• Direct sequencing of the ASXL1 gene was performed.
• The study included 88 unrelated Tunisian and French families with aggregated hematological malignancies.
• In silico analysis was used to predict the effect of identified variants on the ASXL1 protein.

Main Results:

• A novel germline missense substitution, p.Arg402Gln, was identified in two related Tunisian patients.
• This p.Arg402Gln variant is reported for the first time in non-Hodgkin lymphoma.
• The variant was absent in 200 control chromosomes, and in silico analysis predicted a potentially deleterious effect on the ASXL1 protein.

Conclusions:

• The ASXL1 gene may be involved in familial hematological malignancies.
• The identified p.Arg402Gln variant warrants consideration due to its predicted damaging effect.
• Further functional assays are recommended to investigate the biological significance of this variant.