A FISH study of variant Philadelphia rearrangements
A FISH study of variant Philadelphia rearrangements
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DOI：
10.1016/s0165-4608(99)00187-9
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发表时间：
2000-04-15
影响因子：
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通讯作者：
Sulcova, V
中科院分区：
文献类型：
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作者：
Reddy, KS;Sulcova, V
使用MBCR/ABL、mBCR/ABL或DBCR/ABL探针通过荧光原位杂交（FISH）研究了总共39个变体费城（Ph）易位。7例无BCP/ABL融合信号。在32例融合阳性病例中，5例为涉及22号染色体和除9号染色体外的另一条染色体的简单变异; 23例为涉及22号、9号和第三条染色体（18例）或22号、9号和另外两条染色体（4例）的复杂变异。4例检出掩蔽Ph重排。1例为Ph染色体模拟物。荧光原位杂交已成为一种广泛使用的研究Ph重排的方法。目前使用的最新探头是DBCR/ABL（双倒数BCR/ABL信号）。该探针的预期模式是正常9上的一个绿色ABL信号（1G），正常22上的一个红色BCR信号（1 R），以及分别在导数22和导数9上的两个融合信号，BCR/ABL和ABL/BCR（2F）。只要存在融合信号，来自1G 1 R2 F（有时是1G 1 R2 F）的偏离模式就指示变体。然而，在间期分析中，不可能可视化变体重排，并且当观察到涉及至少一个融合信号的异常模式时，应考虑以下可能性。在15个Ph变体中观察到的不同模式进行了描述。在使用DBCR/ABL探针研究的变体中观察到的模式为2G 2 RIF（40%）、1G 1 R2 F（20%）、1G 1 R2 F（20%）、1G 2 R1 F（13.3%）和2G 1 R1 F（6.66%）。每一种模式的形成都涉及一种机制。6例2G 2 R1 F，FISH模式似乎涉及参与染色体上同时断裂的单一协调事件，随后是错配连接。1G 2 R2 F的三个病例最可能是由两个连续的重排引起的。1G 1 R1 F模式表明BCR和ABL断点不同，或者断点处存在缺失，因为未观察到残留信号。在1G 2 R1 F中似乎涉及两个独立的事件，第一个事件是反向隐藏的9，22重排，在一个2G 1 R1 F病例中，合理的解释是ABL插入BCR旁边，同时或顺序易位与另一条染色体。(C)Elsevier Science Inc.，2000. All rights reserved.
A total of 39 variant Philadelphia (Ph) translocations were studied by fluorescence in situ hybridization (FISH) using MBCR/ABL, mBCR/ABL, or DBCR/ABL probes. Seven cases did not have a BCP/ABL fusion signal. Of a fetal of 32 fusion-positive cases, 5 were simple variants involving chromosome 22 and another chromosome apart from chromosome 9; 23 were complex variants involving chromosomes 22, 9, and a third chromosome (18 cases), or 22, 9, and two other chromosomes (4 cases). Masked Ph rearrangements were detected in 4 cases. One case was a Ph chromosome mimic. Fluorescence in situ hybridization has become a widely used method for studying Ph rearrangements. The latest probe that is being used is the DBCR/ABL (double reciprocal BCR/ABL signals). The expected pattern for this probe is one green ABL signal (1G) on the normal 9, one red BCR signal (1R) on the normal 22, and two fusion signals, BCR/ABL and ABL/BCR (2F), on a derivative 22 and a derivative 9, respectively. Deviant patterns from 1G1R2F, and sometimes 1G1R2F, were indicative of a variant, as long as there was a fusion signal. However, in interphase analysis, it is not possible to visualize a variant rearrangement and when a deviant pattern involving at least one fusion signal is observed, the following possibilities should be contemplated. The different patterns observed in fifteen Ph variants are described. The patterns observed in variants studied with the DBCR/ABL probe were 2G2RIF (40%), 1G1R2F (20%), 1G1R2F (20%), 1G2R1F (13.3%), and 2G1R1F (6.66%). A single mechanism is involved in the formation of each of these patterns. A 2G2R1F, FISH pattern in 6 cases appears to involve a single concerted event of simultaneous breaks on the participating chromosomes followed by mismatched joining. The three cases with 1G2R2F most probably arose by two sequential rearrangements. The 1G1R1F pattern suggests that either the BCR and ABL breakpoints are different, or there are deletions at the breakpoints, because residual signals are not observed. Two independent events appear to be involved in 1G2R1F with a reverse cryptic 9,22 rearrangement as the first event, in one case of 2G1R1F, the plausible explanation is an insertion of ABL next to BCR and either a simultaneous or a sequential translocation with another chromosome. (C) Elsevier Science Inc., 2000. All rights reserved.