Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones
Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones
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DOI：
10.1038/sj.leu.2402188
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发表时间：
2001-08
期刊：
影响因子：
11.4
通讯作者：
Yuko Sato;Hirofumi Kobayashi;Y. Suto;Harold J. Olney;Elizabeth M. Davis;H. Super;R. Espinosa;M. Beau;Janet D. Rowley
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文献类型：
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作者：
Yuko Sato;Hirofumi Kobayashi;Y. Suto;Harold J. Olney;Elizabeth M. Davis;H. Super;R. Espinosa;M. Beau;Janet D. Rowley
通过对70例淋巴和髓系恶性血液病患者的中期细胞进行荧光原位杂交(FISH)分析，发现9例患者(4例淋巴系统恶性肿瘤、4例髓系恶性肿瘤和1例双表型白血病)的染色体重排比我们从常规细胞遗传学研究中预期的要复杂。在6名患者中，12P的小片段发生了多个断裂，随后这些片段易位并插入到其他染色体中，有时插入到意想不到的区域。在三名患者中，额外的染色体断裂导致了一个亚克隆，根据细胞遗传学分析，该亚克隆在细胞遗传学上与每个患者的主克隆无法区分。这些微妙的分子事件仅在覆盖TEL/ETV6和KIP1/CDKN1B的区域中检测到。9名患者中有7名有化疗/放疗病史；所有患者都表现出复杂的核型，尽管他们是新诊断的白血病。有5名患者的存活数据可用，所有患者的存活时间都不到6个月。这些发现表明，12p13区域，特别是上述区域，在遗传上是不稳定和脆弱的。化疗/放射治疗中使用的诱变剂很可能导致多个染色体断裂，并与预后极差的一组患者有关。
During fluorescence in situ hybridization (FISH) analysis of metaphase cells from 70 patients with lymphoid and myeloid hematologic malignancies and chromosomal rearrangements involving band 12p13, we identified nine patients (four with lymphoid malignancies, four with myeloid malignancies and one with biphenotypic leukemia) who showed more complicated rearrangements than we had expected from conventional cytogenetic study. In six patients, multiple breaks occurred in small segments of 12p with subsequent translocations and insertions of these segments into other chromosomes, sometimes to unexpected regions. In three patients additional chromosome breaks resulted in a sub-clone which was cytogenetically indistinguishable from the main clone in each patient based on the cytogenetic analysis. These subtle molecular events were detected exclusively in a region covering TEL/ETV6 and KIP1/CDKN1B. Seven of nine had a previous history of chemo/radiotherapy; all the patients showed complex karyotypes, even though they were newly diagnosed with leukemia. Survival data were available in five patients, and all survived less than 6 months. These findings suggest that the 12p13 region, especially the above-mentioned region, is genetically unstable and fragile. It is likely that multiple chromosome breaks were induced through mutagens used in chemo/radiotherapy, and are associated with a sub-group of patients with an extremely bad prognosis.