Genomic features do not account for differences in multiple myeloma risk by ancestry
Studies have reported conflicting findings regarding the contribution of germline variants or somatic genomic drivers to racial disparities in multiple myeloma (MM). To comprehensively investigate somatic drivers in relation to inherited genetics in MM, we combined newly sequenced whole-genome sequencing data with publicly available datasets (total n = 1,286). Overall, we did not identify germline or somatic genomic differences that explain the different risk of developing MM between patients with genetic similarity to African (AFR) or European (EUR) reference populations. A difference in the detectability and timing of APOBEC-associated and germinal center mutational activity was observed. Integrating epidemiological data and mutational signature-based temporal estimates, we challenge the assumption that individuals in the AFR group develop MM at a younger age. Finally, we demonstrate that, with equal access to efficacious therapies, patients in the AFR and EUR groups have equivalent clinical outcomes.
Authors
- Benjamin T. Diamond (ORCID: https://orcid.org/0000-0002-8638-9365)
- Zoe Steinsnyder (ORCID: https://orcid.org/0000-0001-6156-1694)
- Kylee H. Maclachlan (ORCID: https://orcid.org/0000-0001-7873-4854)
- Saad Z. Usmani (ORCID: https://orcid.org/0000-0002-5484-8731)
- Tala Shekarkhand (ORCID: https://orcid.org/0000-0002-1404-4771)
- Eileen M. Boyle (ORCID: https://orcid.org/0000-0001-8791-1744)
- Malin L. Hultcrantz (ORCID: https://orcid.org/0000-0002-9045-6495)
- Urvi Ashok Shah (ORCID: https://orcid.org/0000-0001-8419-1091)
- Hongwei Tang (ORCID: https://orcid.org/0000-0002-2053-788X)
- Ahmet Doǧan (ORCID: https://orcid.org/0000-0001-6576-5256)
- Nicolas Robine (ORCID: https://orcid.org/0000-0001-5698-8183)
- Dylan Gagler (ORCID: https://orcid.org/0000-0003-0333-3989)
- Alexander M. Lesokhin (ORCID: https://orcid.org/0000-0001-9321-702X)
- Faith E. Davies (ORCID: https://orcid.org/0000-0002-3971-2393)
- Linda Banovic Baughn (ORCID: https://orcid.org/0000-0001-5229-4897)
- Timothy R. Chu (ORCID: https://orcid.org/0000-0002-9724-9739)
- Zalman Vaksman (ORCID: https://orcid.org/0000-0001-5121-8657)
- Bachisio Ziccheddu (ORCID: https://orcid.org/0000-0002-2746-0053)
- Elizabeth Brown (ORCID: https://orcid.org/0000-0003-4498-7858)
- Yanming Zhang (ORCID: https://orcid.org/0000-0001-6138-6080)
- Niels Weinhold (ORCID: https://orcid.org/0000-0002-5464-3234)
- Patrick Blaney (ORCID: https://orcid.org/0000-0002-9319-8866)
- Hani Hassoun (ORCID: https://orcid.org/0000-0002-2036-1749)
- Sham Mailankody (ORCID: https://orcid.org/0000-0002-2815-9561)
- Neha Korde (ORCID: https://orcid.org/0000-0002-5538-4318)
- Marios Papadimitriou (ORCID: https://orcid.org/0009-0009-1852-3495)
- Marc S. Raab (ORCID: https://orcid.org/0000-0003-4181-6922)
- Ola Landgren (ORCID: https://orcid.org/0000-0001-6485-4839)
- Huihuang Yan (ORCID: https://orcid.org/0000-0003-0756-2922)
- Carlyn Rose C. Tan (ORCID: https://orcid.org/0000-0001-7922-2594)
- Francesco Maura (ORCID: https://orcid.org/0000-0002-5017-1620)
- Gareth J. Morgan (ORCID: https://orcid.org/0000-0002-4271-6360)
- Lara Winterkorn (ORCID: https://orcid.org/0009-0004-2629-7778)
- Robert Cimera
- Alexandra M. Poos (ORCID: https://orcid.org/0009-0009-4325-3933)
Institutions
- Mayo Clinic (US)
- Memorial Sloan Kettering Cancer Center (US)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- NYU Langone Health (US)
- Mayo Clinic in Arizona (US)
- Netherlands Comprehensive Cancer Organisation (NL)
- The London College (GB)
- Mayo Clinic in Florida (US)
- New York Genome Center (US)
- Sylvester Comprehensive Cancer Center (US)
- University College London (GB)
- University of Arkansas for Medical Sciences (US)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2026-06-12
- DOI
- https://doi.org/10.1158/2643-3230.bcd-25-0259
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00