Caligiuri M A, Strout M P, Schichman S A, Mrózek K, Arthur D C, Herzig G P, Baer M R, Schiffer C A, Heinonen K, Knuutila S, Nousiainen T, Ruutu T, Block A W, Schulman P, Pedersen-Bjergaard J, Croce C M, Bloomfield C D
Division of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Cancer Res. 1996 Mar 15;56(6):1418-25.
Gains of a single chromosome are frequent cytogenic findings in human cancer, but no molecular rearrangement has been consistently associated with any trisomy. In acute myeloid leukemia (AML), trisomy 11 (+11) occurring as a sole abnormality is the third most common trisomy. We have shown that the ALL1 gene, located at 11q23, can be rearranged as a result of a partial tandem duplication in two such cases of AML. To test the hypothesis that the partial tandem duplication of ALL1 is the recurrent molecular defect in cases of AML presenting with +11 as a sole cytogenic abnormality, we performed Southern analysis and PCR for defects of ALL1 in 17 cases of AML and one case of myelodysplastic syndrome with +11 or +11q but without cytogenic evidence of a structural abnormality involving 11q23. Twelve cases (67%) had rearrangement of ALL1, including 10 of 11 patients (91%) with +11 as a sole abnormality and 2 of 7 cases (29%) with +11 and other aberrations; all were classified as FAB M1 or M2. In 10 of the 12 cases, material was available for additional characterization; a partial tandem duplication of ALL1 was detected in each of these 10 cases (100%). Four cases demonstrated previously unreported duplications, two of which were detectable only by reverse transcription-PCR. Four patients with the ALL1 duplication also displayed a loss of material from 7q, suggesting an association between these two findings. We conclude that the partial tandem duplication of ALL1 is present in most, if not all, cases of AML with +11 as a sole abnormality, and can be found in cases of AML with +11 or +11q accompanied by other cytogenic abnormalities. The duplication is more prevalent in AML than was recognized previously in part because its size and location vary considerably, requiring a variety of molecular probes for detection. Our finding of the ALL1 duplication as a consistent defect in patients with +11 represents the first identification of a specific gene rearrangement associated with recurrent trisomy in human cancer.
单个染色体的增加是人类癌症中常见的细胞遗传学发现，但尚未发现有任何分子重排与任何三体性始终相关。在急性髓系白血病（AML）中，作为唯一异常出现的三体11（+11）是第三常见的三体性。我们已经表明，位于11q23的ALL1基因，在两例此类AML病例中可因部分串联重复而发生重排。为了检验ALL1部分串联重复是AML病例中以+11作为唯一细胞遗传学异常的复发性分子缺陷这一假说，我们对17例AML病例和1例伴有+11或+11q但无涉及11q23结构异常的细胞遗传学证据的骨髓增生异常综合征病例进行了ALL1缺陷的Southern分析和PCR检测。12例（67%）存在ALL1重排，包括11例以+11作为唯一异常的患者中的10例（91%）以及7例伴有+11和其他畸变的病例中的2例（29%）；所有病例均被分类为FAB M1或M2。在12例中的10例中，有材料可用于进一步表征；在这10例中的每一例（100%）均检测到ALL1的部分串联重复。4例显示出先前未报道的重复，其中2例仅通过逆转录PCR可检测到。4例ALL1重复的患者还显示7号染色体长臂物质缺失，提示这两个发现之间存在关联。我们得出结论，ALL1的部分串联重复存在于大多数（如果不是全部）以+11作为唯一异常的AML病例中，并且在伴有+11或+11q以及其他细胞遗传学异常的AML病例中也可发现。该重复在AML中比以前认识到的更为普遍，部分原因是其大小和位置差异很大，需要多种分子探针进行检测。我们发现ALL1重复是+11患者中的一致缺陷，这代表了首次鉴定出与人类癌症中复发性三体相关的特定基因重排。
