Homozygous deletions at 9p21 in childhood acute lymphoblastic leukemia detected by microsatellite analysis
Homozygous deletions at 9p21 in childhood acute lymphoblastic leukemia detected by microsatellite analysis
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DOI：
10.1038/sj.leu.2400817
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发表时间：
1997-10-01
期刊：
影响因子：
11.4
通讯作者：
Koeffler, HP
中科院分区：
文献类型：
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作者：
Takeuchi, S;Koike, M;Koeffler, HP
为了更全面地了解9号染色体缺失在儿童急性淋巴细胞白血病（ALL）发生中的作用，我们使用22个高度多态性标记对54例具有匹配正常DNA的原发ALL样本进行了详细的9号染色体缺失定位;并将该信息与我们先前关于这些样品中存在CDKN 2/INK 4A/p16和CDKN 2B/INK 4 B/p15缺失的数据相结合。我们发现染色体臂9 p上有很高频率的杂合性丢失（洛）（31/54例，57%）。与预期的一样，最小的洛缺失区域位于9 p21的D9 S1747和D9 S1748之间，包括CDKN 2/INK 4A/p16，但不包括CDKN 2 B/INK 4 B/p15。在54个样本中有23个（43%）发生了9 p21纯合缺失（11个T-ALL中有7个（64%），45个B-ALL中有16个（36%））。我们检测到7例Southern印迹杂交未检测到的9 p21纯合性缺失，表明微卫星分析在检测纯合性缺失方面的能力。在大多数情况下，纯合性缺失仅限于D9 S1747和CDKN 2B/INK 4 B/p15之间的区域。我们试图确定9 p缺失的机制和时间。在23例9 p21纯合缺失的样本中，21例周围有大的洛缺失。在29例9 p洛缺失中，22例为9 p21纯合缺失。此外，6名患者在诊断和复发时进行了研究，所有6名患者在复发时均显示出与其初始表现相同的9 p21结构（正常，3名患者;半合子缺失，2名患者;纯合子缺失，1名患者）。最后，3名患者（纯合性缺失，1名患者;半合性缺失，2名患者）具有IFN-α：而不是CDKN 2/INK 4A/p16缺失。总之，这些数据进一步强调了9 p21丢失在儿童ALL发展中的重要性。
To gain a fuller understanding of the role of deletions of chromosome 9 in the development of childhood acute lymphoblastic leukemia (ALL), we performed detailed deletional mapping of chromosome 9 in 54 primary ALL samples with matched normal DNA using 22 highly polymorphic markers; and this information was combined with our previous data concerning the presence of deletions of CDKN2/INK4A/p16 and CDKN2B/INK4B/p15 in these samples. We have found a very high frequency of loss of heterozygosity (LOH) (31 of 54 cases (57%)) on chromosome arm 9p. As expected, the smallest region of LOH was between D9S1747 and D9S1748 at 9p21, including CDKN2/INK4A/p16, but excluding CDKN2B/INK4B/p15. Homozygous deletions at 9p21 occurred in 23 of 54 (43%) samples (seven of 11 (64%) T-ALL, 16 of 45 (36%) precursor-B ALL). We detected seven cases of homozygous deletions at 9p21 which had not been detected by Southern blot hybridization, showing the power of microsatellite analysis in detecting homozygous deletions, In most cases, homozygous deletions were limited to the region between D9S1747 and CDKN2B/INK4B/p15. We have attempted to determine the mechanism and timing of 9p deletions. Of the 23 samples with homozygous deletions at 9p21, 21 samples had surrounding large LOH. Of the 29 samples with LOH of 9p, homozygous deletion at 9p21 was identified in 22 cases. In addition, six patients have been studied at diagnosis and relapse, all six showed the same 9p21 structure at relapse (normal, three patients; hemizygous deletions, two patients; homozygous deletion, one patient) as their initial presentation. Finally, three patients (homozygous deletion, one patient; hemizygous deletion, two patients) had the IFN-a: rather than CDKN2/INK4A/p16 deleted. In summary, these data further emphasize the importance of 9p21 loss in the development of childhood ALL.