Impact of copy neutral loss of heterozygosity and total genome aberrations on survival in myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases with varying genetic aberrations. Half of MDS patients have normal karyotype, obscuring the underlying condition indicating a need for new markers for improved diagnostics and prognosis. We performed a retrospective review of sequential MDS patients who underwent chromosomal genetic array testing (CGAT) between November 2008 and March 2014. Total Genomic Aberration (TGA) scores, with and without copy-neutral loss of heterozygosity (cnLOH), were compared to pathology and clinical data. Of 68 MDS participants, 50 patients (73%) had abnormal CGAT results. 32% showedcnLOH, 41% had no cnLOH but displayed copy number aberration (CNAs). Of 26 patients with normal cytogenetics, 46% had clonal abnormalities by CGAT. Abnormal CGAT results were associated with lower overall survival (P=0.04). Overall survival in patients with TGA above the median (68.6 Mb) was significantly inferior to those below the median (HR=2.9, 95% CI=1.3-6.8, P=0.01). Furthermore, there was an observed association between increased TGA and increased dysplastic lineages (Ptrend=0.003). CGAT studies provide important findings that extend beyond current standard testing. Clinical utility of CGAT includes improved diagnostic yield, correlation of extent of TGA and increased dysplastic features, and survival.