Tosi S, Harbott J, Teigler-Schlegel A, Haas O A, Pirc-Danoewinata H, Harrison C J, Biondi A, Cazzaniga G, Kempski H, Scherer S W, Kearney L
MRC Molecular Haematology Unit, Institute of Molecular Medicine, Oxford, U.K.
Genes Chromosomes Cancer. 2000 Dec;29(4):325-32. doi: 10.1002/1098-2264(2000)9999:9999<::aid-gcc1039>3.0.co;2-9.
The ETV6 gene is rearranged as a result of translocations involving a wide variety of chromosomal partners. To date, 12 partner genes for ETV6 have been cloned, and a further 23 chromosomal regions have been described. We previously identified a cryptic t(7;12) with ETV6 involvement in two cases of infant leukemia. The finding of a third case of t(7;12), also in an infant, prompted a more focussed search based on the common features found in these patients and those reported in the literature. The selection criteria were age at diagnosis < 20 months and the presence of +19 and/or +8 in the karyotype; cases with abnormalities of 7q and/or 12p were also considered. FISH studies using whole chromosome paints and probes for the ETV6 gene revealed a t(7;12) in 10 out of 23 cases studied. Seven of these had evidence of ETV6 rearrangement. Of those with ETV6 involvement, six had a 7q36 and one a 7q22 breakpoint. Importantly, in three cases the 7q36 breakpoint was within the same PAC, suggesting the existence of a new nonrandom translocation. However, in at least one patient the 7q36 breakpoint was different. The identification of the 7q partner genes will determine whether it is the disruption of ETV6 alone, or the formation of fusion genes, that is important for leukemogenesis in these patients. As both 7q36 and 7q22 are critical regions of gene loss in del(7q) leukemias, the identification of partner genes from these regions may also be important in understanding the pathogenesis of these diseases.
由于涉及多种染色体伙伴的易位，ETV6基因发生重排。迄今为止，已克隆出12个ETV6的伙伴基因，另外还描述了23个染色体区域。我们之前在两例婴儿白血病病例中发现了隐匿性t(7;12)且涉及ETV6。在又发现一例同样是婴儿的t(7;12)病例后，基于这些患者以及文献报道中发现的共同特征，我们展开了更有针对性的研究。选择标准为诊断时年龄<20个月且核型中存在+19和/或+8；也考虑7q和/或12p异常的病例。使用全染色体涂染探针和ETV6基因探针进行的荧光原位杂交（FISH）研究显示，在23例研究病例中有10例存在t(7;12)。其中7例有ETV6重排的证据。在那些涉及ETV6的病例中，6例的断点在7q36，1例在7q22。重要的是，在3例中7q36断点位于同一个P1人工染色体（PAC）内，提示存在一种新的非随机易位。然而，至少有1例患者的7q36断点不同。确定7号染色体的伙伴基因将决定对于这些患者白血病发生而言，是单独ETV6的破坏还是融合基因的形成更为重要。由于7q36和7q22都是7号染色体长臂缺失（del(7q)）白血病中基因缺失的关键区域，从这些区域鉴定伙伴基因对于理解这些疾病的发病机制可能也很重要。
