Iolascon A, Faienza M F, Coppola B, Moretti A, Basso G, Amaru R, Viganò G, Biondi A
Dipartimento di Biomedicina dell'Eta Evolutiva Universita di Bari, Italy.
Leukemia. 1997 Mar;11(3):359-63. doi: 10.1038/sj.leu.2400596.
Deletions and chromosomal translocations involving the 1p32 region, are frequently observed in T cell acute lymphoblastic leukemia (T-ALL). One of the most common genetic changes is the breakage of the TAL1 gene, which was originally described to be involved in the T-ALL carrying the t(1;14)(p32;q11) translocation. Site-specific deletions in the TAL1 gene are reported to occur in 12-26% of T-ALL with apparently normal karyotype. In order to investigate the presence of other subkaryotypic abnormalities involving the 1p32 chromosomal region, where TAL1 gene is mapped, we assessed losses of heterozygosity (LOH) for microsatellite markers, in a series of 22 children with T-ALL. Microsatellite polymorphic markers flanking the TAL1 gene (D1S211, D1S197, D1S200 and D1S220) were analyzed to detect LOH. Eight patients displayed LOH for at least one of the markers, suggesting the existence of hot spot regions at the short arm of chromosome 1. Two out of 11 with no molecular evidences of TAL1 gene involvement, compared to six out of 11 in the group of TAL1 rearranged gene, showed LOH at 1p32. TAL1 gene rearrangements and clonal LOH may represent two independent events, but could be related to the same causes. For the first time this study provides evidences that LOH at 1p32 region, occurs in T-ALL in the same region known to be involved in chromosomal deletions and translocations. LOH mapping may help to define the location of a new putative tumor-suppressor gene implicated in the transformation and progression of children T-ALL.
涉及1p32区域的缺失和染色体易位在T细胞急性淋巴细胞白血病（T-ALL）中经常被观察到。最常见的基因变化之一是TAL1基因的断裂，该基因最初被描述与携带t(1;14)(p32;q11)易位的T-ALL有关。据报道，在核型明显正常的T-ALL中，12% - 26%会出现TAL1基因的位点特异性缺失。为了研究涉及TAL1基因所在的1p32染色体区域的其他亚核型异常情况，我们评估了一系列22例儿童T-ALL患者微卫星标记的杂合性缺失（LOH）。分析了TAL1基因侧翼的微卫星多态性标记（D1S211、D1S197、D1S200和D1S220）以检测LOH。8例患者至少有一个标记出现LOH，提示1号染色体短臂存在热点区域。在11例无TAL1基因受累分子证据的患者中，有2例出现1p32的LOH，而在TAL1基因重排组的11例患者中有6例出现1p32的LOH。TAL1基因重排和克隆性LOH可能代表两个独立事件，但可能与相同原因有关。本研究首次提供证据表明，1p32区域的LOH发生在T-ALL中已知与染色体缺失和易位有关的同一区域。LOH图谱绘制可能有助于确定一个新的假定肿瘤抑制基因的位置，该基因与儿童T-ALL的转化和进展有关。
