827P - Mutational spectra of the Korean patients with germline predisposition in hematologic malignancies: Five years of experience at a tertiary university hospital

Background

An expanding number of genes predisposing to hematologic malignancies are being discovered by next-generation sequencing (NGS) technology. The 5th edition of the World Health Organization and International Consensus Classification revised their classification of hematologic neoplasms with germline predisposition acknowledging this development. We aimed to identify the mutational spectrum of germline predisposition in hematologic malignancies from Korean patients.

Methods

The study included 444 patients tested for hematologic malignancy panel testing at Pusan National University Yangsan Hospital from January 2019 to December 2022. The assay consisted of 200 genes related to hematologic malignancies and was performed with NGS on genomic DNA extracted from bone marrow specimens or peripheral blood. We identified potential germline variants by retrospective analysis of NGS results. Variant allele frequency > 0.3 of pathogenic or likely pathogenic variants in a known germline predisposition gene was considered potential germline variants. We could not confirm each variant's germline status due to the absence of cultured skin fibroblast specimens.

Results

Thirty-seven (8.33%) patients harbored 38 potential germline variants. DDX41 (21.62%, 8 patients), RUNX1 (10.81%, 4 patients), GATA2 (10.81%, 4 patients), and PAX5 (10.81%, 4 patients) were the most common genes. One patient had 2 variants in the SBDS gene, a compound heterozygote. Frameshift (18 variants, 47.37%) and missense (10 variants, 26.32%) were the main proportion of the 38 potential germline variants.

Conclusions

We found that DDX41, RUNX1, GATA2, and PAX5 are the most common genes in potential germline variants in hematologic malignancies in Korea. This study provides insight into the pathophysiology of germline predisposition in hematologic malignancies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.