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

Mod Pathol. 2018 Apr;31(4):569-580. doi: 10.1038/modpathol.2017.157. Epub 2017 Dec 15.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Child
  • Child, Preschool
  • Chromosome Aberrations*
  • Female
  • Humans
  • Loss of Heterozygosity / genetics*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / mortality
  • Retrospective Studies
  • Young Adult

Substances

  • Biomarkers, Tumor