Genome-wide Copy Number Variations Reveal Distinct Genomic Signatures in an Admixed Brazilian Cohort With Myelodysplastic Neoplasms
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Myelodysplastic neoplasms (MDS) comprise a heterogeneous group of clonal hematopoietic disorders characterized by cytopenias, ineffective hematopoiesis, and a variable risk of progression to acute myeloid leukemia. Although conventional cytogenetic abnormalities are widely used for prognostic stratification, a substantial proportion of patients present with normal karyotypes, suggesting the involvement of submicroscopic genomic alterations. Aim To evaluate the genomic profile of copy number variations (CNVs) in Brazilian patients with MDS and investigate their associations with clinical, cytogenetic, and ancestry-related characteristics. Materials and methods This retro-prospective study included 94 patients diagnosed with MDS at a tertiary referral center in Northeastern Brazil and 94 cancer-free controls. CNVs were identified using high-density SNP microarrays (Axiom™ Precision Medicine Diversity Array), covering approximately 870,000 markers. Analyses included genomic burden assessment, chromosomal distribution, clinicopathological associations, and ancestry inference using ADMIXTURE. Quality control filters were applied to retain high-confidence CNVs, including exclusion of diploid regions, events < 10 kb, segments supported by fewer than 20 markers, and low-intensity signals. Results A total of 44,072 CNVs were identified across the evaluated autosomal chromosomes. Patients with MDS exhibited a significantly higher overall CNV burden than controls (p = 0.01), mainly driven by an increased number of copy number gains (p = 0.01). CNVs in MDS patients also displayed significantly larger genomic sizes (p < 0.05). Copy number gains were more frequently observed on chromosomes 1, 3, 6, 7, 12, 14, 15, 16, 17, 19, and 22, whereas copy number losses predominated on chromosomes 2, 5, 7, and 18. The presence of dysmegakaryopoiesis was associated with a higher total CNV burden (p = 0.019) and increased copy number gains (p = 0.011). Patients with abnormal karyotypes exhibited a greater number of copy number losses (p = 0.002) and larger CNV sizes (p = 0.001). Among the WHO 2022 MDS subtypes, cases harboring del(5q) showed the highest burden of CNVs and genomic losses. Individuals with intermediate levels of Asian ancestry presented a higher overall CNV burden compared with those with low Asian ancestry (p = 0.046). However, no significant differences in ancestry proportions were observed between patients with MDS and controls. Discussion These findings demonstrate increased genomic instability in MDS, with non-random CNV distribution and significant associations with morphological and cytogenetic features. Collectively, the data support CNV burden as a marker of genomic complexity and suggest that genome-wide CNV profiling may complement conventional approaches for biological characterization and risk assessment in MDS. Conclusion Brazilian patients with MDS exhibit a significantly increased CNV burden and larger genomic alterations, with specific chromosomal patterns and associations with clinical and cytogenetic features. Comprehensive genomic profiling may contribute to the identification of novel diagnostic and prognostic biomarkers in MDS. Funding: This study was supported by the National Institute of Science and Technology (INCT), through the INCT T-Bio² – Translational Biodiscovery and Biomodels (grant no. 408566/2024-8).
Institutions: Universidade Federal do Ceará, Hospital de Câncer de Barretos
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223139620