Cavé H, Cacheux V, Raynaud S, Brunie G, Bakkus M, Cochaux P, Preudhomme C, Laï J L, Vilmer E, Grandchamp B
Laboratoire de Biochimie Génétique, Hôpital Robert Debré, Paris, France.
Leukemia. 1997 Sep;11(9):1459-64. doi: 10.1038/sj.leu.2400798.
The presence of ETV6 deletions was investigated in 215 children with acute lymphoblastic leukemia (ALL) using the loss of heterozygosity (LOH) approach. We used four intragenic or juxtagenic microsatellite markers to detect allelic deletions. In this series of unselected patients, LOH of ETV6 markers was found in 23% of cases (6% of T-ALL and 26% of B lineage ALL) confirming that chromosome 12p12-13 deletions represent a major genetic alteration in childhood ALL, frequently missed by cytogenetic analysis. The presence of a t(12;21)(p13;q22) was studied by RT-PCR and/or FISH in a total of 134 patients (125 B lineage ALL, nine T-ALL) including 42 cases with LOH. Thirty-four out of 44 patients (77%) for whom a t(12;21) was observed displayed LOH of the ETV6 markers. When associated with a t(12;21), ETV6 is very likely to be the target of deletions as indicated by the detection of intragenic deletions in three patients. Although deletion of ETV6 and t(12;21) were associated in most patients, in eight cases (six B lineage and two T-ALL) LOH was detected at the ETV6 locus without ETV6-AML1 hybrid RNA. FISH studies conducted in five of these eight patients confirmed the absence of translocation involving ETV6. In such patients, the other allele of ETV6 could be disrupted by either a small deletion, a point mutation, or an epigenetic modification and it will be of interest to study the structure and expression of the remaining allele of ETV6 in these cases. Alternatively, a tumor suppressor gene located close to ETV6 and CDKN1B could be the target of deletions.
采用杂合性缺失（LOH）方法，对215例急性淋巴细胞白血病（ALL）患儿进行了ETV6缺失情况的研究。我们使用四个基因内或基因旁微卫星标记来检测等位基因缺失。在这组未经选择的患者中，23%的病例（T-ALL为6%，B系ALL为26%）发现ETV6标记的LOH，证实12p12 - 13染色体缺失是儿童ALL的主要基因改变，常被细胞遗传学分析遗漏。通过RT-PCR和/或FISH对总共134例患者（125例B系ALL，9例T-ALL）进行了t(12;21)(p13;q22)的研究，其中包括42例有LOH的病例。在观察到t(12;21)的44例患者中，有34例（77%）显示ETV6标记的LOH。当与t(12;21)相关时，如在3例患者中检测到基因内缺失所示，ETV6很可能是缺失的靶点。尽管大多数患者中ETV6缺失与t(12;21)相关，但在8例患者（6例B系和2例T-ALL）中，在ETV6位点检测到LOH，但未检测到ETV6-AML1杂交RNA。对这8例患者中的5例进行的FISH研究证实不存在涉及ETV6的易位。在这些患者中，ETV6的另一个等位基因可能因小缺失、点突变或表观遗传修饰而被破坏，研究这些病例中ETV6剩余等位基因的结构和表达将很有意义。或者，位于ETV6和CDKN1B附近 的一个肿瘤抑制基因可能是缺失的靶点。
