Lishner M, Lalkin A, Klein A, Yarkoni S, Manor Y, Fejgin M, Leytin V, Ravid M, Amiel A
Department of Medicine, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Cancer Genet Cytogenet. 1995 Dec;85(2):118-23. doi: 10.1016/0165-4608(95)00152-2.
The putative oncogenes BCL-1, BCL-2, and BCL-3 are commonly rearranged by translocations to the immunoglobulin genes in B-cell malignancies. However, Southern blotting rarely detected their involvement in chronic lymphocytic leukemia (CLL). This discrepancy could stem from some unique features of the oncogenesis of CLL or be due to shortcomings of Southern blotting. We have therefore evaluated the role of fluorescence in situ hybridization (FISH) in the detection of these oncogenes in CLL. Twenty consecutive CLL patients were studied by FISH for the detection of BCL-1, BCL-2, or BCL-3 rearrangement and for the presence of trisomy 12. Selected patients were also evaluated by classical cytogenetic techniques and by Southern blot analysis. Juxtaposition of JH and BCL-1 was demonstrated in 10 (50%), BCL-2 in three (15%), and BCL-3 in four (20%) of the patients. Trisomy 12 was detected by FISH in 11 (55%) patients. The coexistence of trisomy 12 and translocation of the BCL-1 oncogene was common. Three of the patients had chromosomal aberrations compatible with those detected by FISH. In contrast, in none of the five patients selected by their positive FISH findings was a rearrangement demonstrated by Southern blotting. We conclude that FISH is a sensitive method for the detection of oncogene involvement in CLL. Mainly BCL-1, but also BCL-2 and BCL-3, are commonly translocated to the immunoglobulin heavy chain locus on chromosome 14. These translocations are often associated with trisomy 12. These findings indicate that the BCL oncogenes are commonly involved in CLL and lend support to the multi-hit theory of cancer development.
假定的癌基因BCL-1、BCL-2和BCL-3在B细胞恶性肿瘤中通常通过易位与免疫球蛋白基因重排。然而，Southern印迹法很少检测到它们参与慢性淋巴细胞白血病（CLL）。这种差异可能源于CLL肿瘤发生的一些独特特征，或者是由于Southern印迹法的缺点。因此，我们评估了荧光原位杂交（FISH）在检测CLL中这些癌基因的作用。通过FISH对20例连续的CLL患者进行研究，以检测BCL-1、BCL-2或BCL-3重排以及12号染色体三体的存在。选定的患者还通过经典细胞遗传学技术和Southern印迹分析进行评估。在10例（50%）患者中证实了JH与BCL-1并列，3例（15%）患者中证实了BCL-2并列，4例（20%）患者中证实了BCL-3并列。通过FISH在11例（55%）患者中检测到12号染色体三体。12号染色体三体与BCL-1癌基因易位并存很常见。其中3例患者的染色体畸变与FISH检测到的相符。相反，在根据FISH阳性结果选定的5例患者中，Southern印迹法均未显示重排。我们得出结论，FISH是检测癌基因参与CLL的一种敏感方法。主要是BCL-1，还有BCL-2和BCL-3，通常易位至14号染色体上的免疫球蛋白重链基因座。这些易位常与12号染色体三体相关。这些发现表明BCL癌基因通常参与CLL，并支持癌症发展的多步骤理论。
