Kolquist Kathryn A, Schultz Roger A, Furrow Aubry, Brown Theresa C, Han Jin-Yeong, Campbell Lynda J, Wall Meaghan, Slovak Marilyn L, Shaffer Lisa G, Ballif Blake C
Sacred Heart Medical Center, Spokane, WA, USA.
Cancer Genet. 2011 Nov;204(11):603-28. doi: 10.1016/j.cancergen.2011.10.004.
The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis, cytopenias, and a risk of transformation to acute myeloid leukemia (AML). However, only approximately 50% of primary MDS patients show clonal cytogenetic aberrations. To determine whether high-resolution microarray analysis would reveal new or additional aberrations, we analyzed 35 samples derived from patients with a diagnosis or suspicion of MDS and abnormal karyotypes. We used a whole-genome oligonucleotide microarray with targeted coverage of approximately 1900 genes associated with hematologic and other cancers. Clinically relevant copy number aberrations (CNAs) were identified by microarray-based comparative genomic hybridization (aCGH) in all samples (range 1-31, median 5). In 28 of 35 samples (80%), aCGH revealed new cytogenetic aberrations not seen by karyotype or fluorescence in situ hybridization (FISH). Furthermore, 132 cryptic aberrations (≤5 Mb) were identified in 25 cases (71.4%) including deletions of NF1, RUNX1, RASSF1, CCND1, TET2, DNMT3A, HRAS, PDGFRA and FIP1L1. Additionally, aCGH clarified known complex aberrations in 17 of 35 samples (48.6%). Finally, our results using whole-genome arrays with higher density coverage targeted to cancer features demonstrate the usefulness of arrays to identify rare and cryptic recurring imbalances that may prove to be significant in disease progression or transformation to AML and may improve the suitability or efficacy of molecularly targeted therapy.
骨髓增生异常综合征（MDS）是一组异质性克隆性疾病，其特征为造血无效、血细胞减少以及转化为急性髓系白血病（AML）的风险。然而，只有约50%的原发性MDS患者显示克隆性细胞遗传学异常。为了确定高分辨率微阵列分析是否会揭示新的或额外的异常，我们分析了35份来自诊断或疑似MDS且核型异常患者的样本。我们使用了全基因组寡核苷酸微阵列，其靶向覆盖约1900个与血液系统及其他癌症相关的基因。通过基于微阵列的比较基因组杂交（aCGH）在所有样本中均鉴定出临床相关的拷贝数异常（CNA）（范围为1 - 31，中位数为5）。在35份样本中的28份（80%）中，aCGH揭示了核型分析或荧光原位杂交（FISH）未发现的新的细胞遗传学异常。此外，在25例（71.4%）中鉴定出132处隐匿性异常（≤5 Mb），包括NF1、RUNX1、RASSF1、CCND1、TET2、DNMT3A、HRAS、PDGFRA和FIP1L1的缺失。另外，aCGH在35份样本中的17份（48.6%）中明确了已知的复杂异常。最后，我们使用针对癌症特征具有更高密度覆盖的全基因组阵列所得到的结果表明，该阵列有助于识别罕见和隐匿性复发性失衡，这些失衡可能在疾病进展或转化为AML过程中具有重要意义，并且可能提高分子靶向治疗的适用性或疗效。
