Cetin Zafer, Yakut Sezin, Karadogan Ihsan, Kupesiz Alphan, Timuragaoglu Aysen, Salim Ozan, Tezcan Gulsun, Alanoglu Guchan, Ozbalci Demircan, Hazar Volkan, Yesilipek Mehmet Akif, Undar Levent, Luleci Guven, Berker Sibel
Department of Medical Biology, Akdeniz University, Antalya, Turkey.
Genet Test Mol Biomarkers. 2012 May;16(5):318-23. doi: 10.1089/gtmb.2011.0186. Epub 2012 Feb 23.
A reciprocal translocation between chromosomes 9 and 22 creates oncogenic BCR/ABL fusion in the breakpoint region of the derivative chromosome 22. The aim of this study was to evaluate the importance of atypical fluorescence in situ hybridization (FISH) signal patterns in pediatric and adult acute lymphoblastic leukemia (ALL) cases. We evaluated t(9;22) translocation in 208 cases with ALL (294 tests), including 139 childhood and 69 adult cases by FISH technique using BCR/ABL extra signal (ES) probe. FISH signal patterns observed in pediatric ALL cases were as follows; Major-BCR/ABL (M-BCR/ABL) (1.4%), minor-BCR/ABL (m-BCR/ABL) (3.6%), trisomy 9 (4.3%), trisomy 22 (4.3%), trisomy or tetrasomy of both chromosomes 9 and 22 (2.9%), monosomy 9 (1.4%), monosomy 22 (0.7%), ABL gene amplification (1.4%), derivative chromosome 9 deletion (1.4%), and extra copies of the Philadelphia chromosome (1.4%). FISH signal patterns observed in adult ALL cases were as follows; M-BCR/ABL (5.8%), m-BCR/ABL (11.6%), two different cell clones with major and minor BCR/ABL signal pattern (2.9%), extra copies of Philadelphia chromosome (4.3%), derivative chromosome 9 deletion (1.4%), trisomy 9 (2.9%), tetraploidy (1.4%), monosomy 9 (1.4%), trisomy 22 (1.4%), and coexistence of both trisomy 22 and monosomy 9 (1.4%). Trisomy 9, trisomy 22, and polyploidy of chromosomes 9 and 22 were specific atypical FISH signal patterns for childhood B cell acute lymphoblastic leukemia (B-ALL) patients. However, monosomy 9 and ABL gene amplification were highly specific for childhood T cell acute lymphoblastic leukemia (T-ALL) patients. Our report presents the correlation between atypical FISH signal patterns and clinical findings of a large group of ALL cases.
9号和22号染色体之间的相互易位在衍生22号染色体的断点区域产生致癌性BCR/ABL融合基因。本研究的目的是评估非典型荧光原位杂交(FISH)信号模式在儿童和成人急性淋巴细胞白血病(ALL)病例中的重要性。我们使用BCR/ABL额外信号(ES)探针,通过FISH技术评估了208例ALL患者(共294次检测)中的t(9;22)易位情况,其中包括139例儿童病例和69例成人病例。在儿童ALL病例中观察到的FISH信号模式如下:主要BCR/ABL(M-BCR/ABL)(1.4%)、次要BCR/ABL(m-BCR/ABL)(3.6%)、9号染色体三体(4.3%)、22号染色体三体(4.3%)、9号和22号染色体三体或四体(2.9%)、9号染色体单体(1.4%)、22号染色体单体(0.7%)、ABL基因扩增(1.4%)、衍生9号染色体缺失(1.4%)以及费城染色体额外拷贝(1.4%)。在成人ALL病例中观察到的FISH信号模式如下:M-BCR/ABL(5.8%)、m-BCR/ABL(11.6%)、具有主要和次要BCR/ABL信号模式的两种不同细胞克隆(2.9%)、费城染色体额外拷贝(4.3%)、衍生9号染色体缺失(1.4%)、9号染色体三体(2.9%)、四倍体(1.4%)、9号染色体单体(1.4%)、22号染色体三体(1.4%)以及22号染色体三体和9号染色体单体共存(1.4%)。9号染色体三体、22号染色体三体以及9号和22号染色体多倍体是儿童B细胞急性淋巴细胞白血病(B-ALL)患者特有的非典型FISH信号模式。然而,9号染色体单体和ABL基因扩增对儿童T细胞急性淋巴细胞白血病(T-ALL)患者具有高度特异性。我们的报告展示了一大组ALL病例中非典型FISH信号模式与临床发现之间的相关性。