Application of single nucleotide polymorphism array (SNP array) derived median copy number state for monitoring the clonal burden of the chromosomal aberrations in myelodysplastic neoplasms.

OBJECTIVES: Our study integrates SNP array and metaphase cytogenetics (MC) to decode clonal architecture in myelodysplastic syndromes (MDS) and related disorders.

METHODS: We retrospectively analyzed chromosomal aberrations in 33 patients diagnosed with MDS and related disorders by both SNP array and MC, of whom ten were detected with chromosomal copy number variations (CNVs) by MC. SNP array was used to quantify the clonal burden of CNVs using the metric median copy number state.

RESULTS: We found that SNP array-derived median copy number state was associated with the abnormal/total ratio by MC, implying the utility of the SNP array derived indicator for detecting the clonal burden of chromosomal CNVs in MDS and related disorders. In our cohort, patients with isolated trisomy 8 clones showed relatively low clonal burden and more stable outcomes compared with those having trisomy 8 in complex karyotypes, whereas +1/1q + clones, even as sole lesions, were associated with aggressive progression. The higher clonal burden of trisomy 8 (elevated median copy number deviations compared to other lesions) was found in patients with complex karyotypes and poor prognosis, which further supported the staged evolution theory and provided a new perspective for studying the development of chromosomal abnormalities in myelodysplastic neoplasms.

CONCLUSION: The SNP array may serve as a novel tool for precision disease management, enabling early identification of high-risk clones and refinement of prognostic assessment in myelodysplastic neoplasms.