Meléndez B, Santos J, Fernández-Piqueras J
Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
Oncogene. 1999 Jul 15;18(28):4166-9. doi: 10.1038/sj.onc.1202826.
Recent studies in our laboratory reported frequent loss of heterozygosity (LOH) on mouse chromosome 4 in T-cell lymphomas, identifying three candidate tumor suppressor regions (TLSR1-3). To determine the possible existence of other tumor suppressor gene loci on the proximal-mid part of chromosome 4 and to clarify whether the p16(INK4a) (alpha and beta) and p15(INK4b) genes are the inactivation targets of deletion at TLSR1, we have tested 73 gamma-radiation-induced T-cell lymphomas of F1 hybrid mice by LOH analysis. Frequent LOH was found at the INK4a and INK4b loci and the surrounding markers D4Mit77, D4Mit245 and D4Wsm1. In addition, we identified two distinct regions of significant allelic losses in the proximal-mid part of chromosome 4, defined by the markers D4Mit116 (TLSR4) and D4Mit21 (TLSR5). Taken together, this evidence and our previous data indicate the existence of at least five different candidate sites for tumor suppressor genes on chromosome 4, thus revealing a main role for this chromosome in the development of mouse T-cell lymphomas.
我们实验室最近的研究报告称，在T细胞淋巴瘤中，小鼠4号染色体上频繁发生杂合性缺失（LOH），确定了三个候选肿瘤抑制区域（TLSR1 - 3）。为了确定4号染色体近端 - 中部是否可能存在其他肿瘤抑制基因位点，并阐明p16(INK4a)（α和β）和p15(INK4b)基因是否是TLSR1处缺失的失活靶点，我们通过LOH分析检测了73例F1杂交小鼠经γ射线诱导产生的T细胞淋巴瘤。在INK4a和INK4b基因座以及周围标记D4Mit77、D4Mit245和D4Wsm1处发现频繁的LOH。此外，我们在4号染色体近端 - 中部确定了两个明显的等位基因显著缺失区域，由标记D4Mit116（TLSR4）和D4Mit21（TLSR5）界定。综上所述，这些证据和我们之前的数据表明，4号染色体上至少存在五个不同的肿瘤抑制基因候选位点，从而揭示了该染色体在小鼠T细胞淋巴瘤发展中的主要作用。
