Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Pathology, University of Washington, Seattle, WA, USA.
Mod Pathol. 2018 Apr;31(4):569-580. doi: 10.1038/modpathol.2017.157. Epub 2017 Dec 15.
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.
骨髓增生异常综合征（MDS）是一组具有不同遗传异常的异质性疾病。一半的 MDS 患者具有正常核型，掩盖了潜在的情况，表明需要新的标记物来改善诊断和预后。我们对 2008 年 11 月至 2014 年 3 月间接受染色体遗传阵列检测（CGAT）的连续 MDS 患者进行了回顾性研究。比较了总基因组异常（TGA）评分，包括有无拷贝中性杂合性丢失（cnLOH），与病理学和临床数据进行了比较。在 68 名 MDS 参与者中，有 50 名患者（73%）的 CGAT 结果异常。32%的患者显示 cnLOH，41%的患者无 cnLOH，但显示拷贝数异常（CNAs）。在 26 名核型正常的患者中，46%的患者通过 CGAT 存在克隆异常。异常 CGAT 结果与总生存期较短相关（P=0.04）。TGA 高于中位数（68.6 Mb）的患者的总体生存率明显低于中位数以下的患者（HR=2.9，95%CI=1.3-6.8，P=0.01）。此外，TGA 增加与发育异常谱系增加之间存在观察到的关联（Ptrend=0.003）。CGAT 研究提供了超出当前标准检测的重要发现。CGAT 的临床应用包括提高诊断率、TGA 程度和发育异常特征的相关性以及生存率的提高。
