A newly published, large case–control study shows that germline mutations in specific DNA damage response genes significantly increase the risk of developing multiple myeloma. The article appeared in the January issue of the Journal of Hematology and Oncology.
By analyzing more than 3400 patients with multiple myeloma and over 320000 cancer-free individuals, the researchers found that rare pathogenic inherited variants were significantly more common in myeloma patients than in controls.
Five genes emerged as clearly associated with increased myeloma risk: TP53, ATM, CHEK2, KDM1A and ARID1A. Overall, around 5% of myeloma patients carried one of these pathogenic germline variants, a frequency that is comparable to cancers where genetic testing is already included in routine protocols.
The study also found that patients carrying TP53 or ATM germline mutations had significantly worse overall survival than non-carriers, and that the carriers of certain mutations, particularly KDM1A, tended to develop myeloma at a younger age than the typical population average; the authors conclude that inherited defects in DNA repair pathways contribute not only to myeloma risk, but also to disease aggressiveness.
The practical implications for the diagnosis and treatment of multiple myeloma are significant: in fact, germline genetic testingmight become a very useful resource, particularly in younger patients or those with a family history.
At 4bases, we focus on making available gene panels that can support a variety of genetic profile questions; this is the case with HEMATO pro, a CE-IVD kit designed for the analysis of complex genomic variants associated with Lymphoid and Myeloid Diseases.
With the analysis of 146 relevant genes frequently mutated in hematologic malignancies, the kit is validated for both germline and somatic analysis (SNVs, indels, CNVs and ITD) of DNA extracted from blood samples.
Eager to learn more details? Read the full study!
Multiple myeloma risk linked to DNA damage response genes
Conry et al., J Hematol Oncol. 2026 Jan 6;19:10; doi: 10.1186/s13045-025-01776-1
