Mrózek Krzysztof, Heinonen Kristiina, Theil Karl S, Bloomfield Clara D
Division of Hematology and Oncology and the Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210-1228, USA.
Genes Chromosomes Cancer. 2002 Jun;34(2):137-53. doi: 10.1002/gcc.10027.
We used spectral karyotyping (SKY) to study 29 adults with acute myeloid leukemia and a complex karyotype containing one to nine abnormalities that were not fully identifiable by G-banding. SKY showed the origin of rings and unidentified material in unbalanced translocations in all cases and the origin of markers in most, allowing reinterpretation of 136 aberrations and discovery of three aberrations hidden in normal chromosomes. SKY confirmed 10 and refined the interpretation of three balanced aberrations recognized by G-banding and identified another nine balanced aberrations, including a novel translocation involving the RUNX1 gene. Eleven of 32 deletions found by G-banding were shown to be cryptic translocations or insertions, including three of four chromosome 3 deletions, two of three del(7q), and two of 12 del(5q). Of the 92 chromosomes deemed lost entirely by G-banding, 63 (68%) were shown to be involved in structural aberrations. This was especially true for -21 (eight of eight patients), -5 (five of six patients), -20 (seven of nine patients), and -18 (six of 12 patients). Unexpectedly, SKY uncovered a hidden overrepresentation of segments from at least one chromosome in 21 patients. The most frequently overrepresented was 21q, found in eight patients, including four with high-level 21q amplification. Fluorescence in situ hybridization showed that the RUNX1 gene was not the target of amplification in seven of these patients. Also frequently gained were 11q (in seven patients, including three with high-level MLL gene amplification) and 22q (in seven patients). We conclude that SKY considerably enhances the accuracy of karyotype interpretation, and that amplification of chromosomal material may play a greater role in leukemogenesis than has been recognized.
我们运用光谱核型分析（SKY）技术，对29例患有急性髓系白血病且具有复杂核型的成年患者进行研究，这些患者的核型包含1至9处异常，通过G显带技术无法完全识别。SKY显示，在所有病例中，不平衡易位中环和无法识别物质的起源，以及大多数病例中标记物的起源，从而使得136处畸变得以重新解释，并发现了隐藏在正常染色体中的3处畸变。SKY证实了10处畸变，并完善了对G显带识别出的3处平衡畸变的解释，还识别出另外9处平衡畸变，包括涉及RUNX1基因的一种新型易位。G显带发现的32处缺失中，有11处被证明是隐匿性易位或插入，包括4处3号染色体缺失中的3处、3处del(7q)中的2处以及12处del(5q)中的2处。在G显带判定完全丢失的92条染色体中，有63条（68%）被证明参与了结构畸变。对于-21（8例患者中的8例）、-5（6例患者中的5例）、-20（9例患者中的7例）和-18（12例患者中的6例）尤其如此。出乎意料的是，SKY在21例患者中发现至少一条染色体的片段存在隐藏的过度表达。最常过度表达的是21q，在8例患者中发现，包括4例高水平21q扩增的患者。荧光原位杂交显示，在这些患者中的7例中，RUNX1基因并非扩增的靶点。同样经常获得的还有11q（在7例患者中，包括3例高水平MLL基因扩增的患者）和22q（在7例患者中）。我们得出结论，SKY显著提高了核型解释的准确性，并且染色体物质的扩增在白血病发生过程中可能发挥比已认识到的更大的作用。
