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TEL和KIP1确定了造血系统恶性肿瘤中12p13上最小的缺失区域。

TEL and KIP1 define the smallest region of deletions on 12p13 in hematopoietic malignancies.

作者信息

Sato Y, Suto Y, Pietenpol J, Golub T R, Gilliland D G, Davis E M, Le Beau M M, Roberts J M, Vogelstein B, Rowley J D

机构信息

Department of Medicine, University of Chicago, IL 60637, USA.

出版信息

Blood. 1995 Aug 15;86(4):1525-33.

PMID:7632960
Abstract

Unbalanced translocations as well as interstitial deletions of the short arm of chromosome 12 [del(12p)] are found as recurring chromosomal changes in a broad spectrum of hematopoietic malignancies. These changes result in the hemizygous deletion of genetic material from 12p. We mapped a yeast artificial chromosome containing the TEL gene, a cosmid contig containing part of TEL and a P1 contig containing the KIP1 gene to 12p13. These probes were used for fluorescence in situ hybridization to analyze samples from 47 patients with various hematologic malignancies who had unbalanced translocations (25 patients) leading to loss of 12p or deletions (22 patients) involving 12p13. The patients had acute lymphoblastic leukemia (8 cases), myelodysplastic syndrome (MDS; 11 cases), acute myeloid leukemia (AML; 10 cases), myeloproliferative disorders (4 cases), therapy-related MDS or AML (7 cases), non-Hodgkin's lymphoma (2 cases), and other hematopoietic malignancies (5 cases). All three probes were hemizygously detected in 26 cases and were completely retained in only 9 cases. In 12 cases probes for one of the two genes were deleted, allowing us to map the smallest region of overlap of these deletions to a small genomic region that is bordered on the telomeric side by the TEL gene and on the centromeric side by KIP1. The genomic distance between TEL and KIP1 is estimated to be about 1 to 2 Mbp.

摘要

不平衡易位以及12号染色体短臂的间质缺失[del(12p)]在多种造血系统恶性肿瘤中作为反复出现的染色体改变被发现。这些改变导致12p遗传物质的半合子缺失。我们将含有TEL基因的酵母人工染色体、含有部分TEL的黏粒重叠群以及含有KIP1基因的P1重叠群定位到12p13。这些探针用于荧光原位杂交,以分析47例患有各种血液系统恶性肿瘤患者的样本,这些患者存在不平衡易位(25例)导致12p缺失或涉及12p13的缺失(22例)。患者患有急性淋巴细胞白血病(8例)、骨髓增生异常综合征(MDS;11例)、急性髓系白血病(AML;10例)、骨髓增殖性疾病(4例)、治疗相关的MDS或AML(7例)、非霍奇金淋巴瘤(2例)以及其他造血系统恶性肿瘤(5例)。在26例中检测到所有三个探针半合子缺失,仅在9例中完全保留。在12例中,两个基因之一的探针缺失,这使我们能够将这些缺失的最小重叠区域定位到一个小的基因组区域,该区域在端粒侧以TEL基因为边界,在着丝粒侧以KIP1基因为边界。TEL和KIP1之间的基因组距离估计约为1至2兆碱基对。

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