SNP array karyotyping allows for the detection of uniparental disomy and cryptic chromosomal abnormalities in MDS/MPD-U and MPD.
SNP array karyotyping allows for the detection of uniparental disomy and cryptic chromosomal abnormalities in MDS/MPD-U and MPD.
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DOI：
10.1371/journal.pone.0001225
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发表时间：
2007-11-21
期刊：
影响因子：
3.7
通讯作者：
Maciejewski JP
中科院分区：
文献类型：
--
作者：
Gondek LP;Dunbar AJ;Szpurka H;McDevitt MA;Maciejewski JP
我们应用单核苷酸多态性阵列（SNP-A）研究非典型骨髓增殖性综合征（MPD）患者的核型异常，包括骨髓增殖性/骨髓增生异常综合征（MPD）患者JAK2 V617F突变和继发性急性髓系白血病（AML）的阳性和阴性重叠。在典型的MPD病例（N = 8）中，作为对照组，纯合V617F突变的患者使用SNP-A显示出明显的9p单系二体（UPD）。与可能的基因组不稳定性一致，在19/30的MDS/MPD-U患者中，我们发现了中期细胞遗传学未发现的额外病变。除了UPD9p，我们还检测到UPD影响其他染色体，包括1(2/30),11(4/30),12（1/30）和22（1/30）。30例患者中有8例转化为AML。在5名进展为AML的V617F+患者中，我们发现SNP-A可以检测两种转化模式：白血病母细胞从携带其他获得性染色体缺陷的野生型jak2前体进化而来，或者从以UPD9p为特征的V617F+突变祖细胞进化而来。基于snp检测MDS/MPD-U的隐性病变可能有助于解释该疾病的临床异质性。
We applied single nucleotide polymorphism arrays (SNP-A) to study karyotypic abnormalities in patients with atypical myeloproliferative syndromes (MPD), including myeloproliferative/myelodysplastic syndrome overlap both positive and negative for the JAK2 V617F mutation and secondary acute myeloid leukemia (AML). In typical MPD cases (N = 8), which served as a control group, those with a homozygous V617F mutation showed clear uniparental disomy (UPD) of 9p using SNP-A. Consistent with possible genomic instability, in 19/30 MDS/MPD-U patients, we found additional lesions not identified by metaphase cytogenetics. In addition to UPD9p, we also have detected UPD affecting other chromosomes, including 1 (2/30), 11 (4/30), 12 (1/30) and 22 (1/30). Transformation to AML was observed in 8/30 patients. In 5 V617F+ patients who progressed to AML, we show that SNP-A can allow for the detection of two modes of transformation: leukemic blasts evolving from either a wild-type jak2 precursor carrying other acquired chromosomal defects, or from a V617F+ mutant progenitor characterized by UPD9p. SNP-A-based detection of cryptic lesions in MDS/MPD-U may help explain the clinical heterogeneity of this disorder.
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影响因子：
4.7
作者：
Andersen, Claus Lindbjerg;Wiuf, Carsten;Orntoft, Torben Falck
通讯作者：
Orntoft, Torben Falck
影响因子：
20.3
作者：
Levine, RL;Loriaux, M;Deininger, MWN
通讯作者：
Deininger, MWN
影响因子：
8
作者：
Lee, JW;Kim, YG;Lee, SH
通讯作者：
Lee, SH
影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
DOI：
10.1016/s0889-8588(03)00087-x
发表时间：
2003-10-01
影响因子：
2.4
作者：
Adeyinka, A;Dewald, GW
通讯作者：
Dewald, GW