Kholodnyuk I, Kost-Alimova M, Kashuba V, Gizatulin R, Szeles A, Stanbridge E J, Zabarovsky E R, Klein G, Imreh S
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Genes Chromosomes Cancer. 1997 Mar;18(3):200-11.
We have previously shown that four markers spanning the 3p24-p21.3 region, THRB, AP20R, D3S1029, and D3S32, were regularly eliminated from three human chromosome 3 (chr3)/mouse microcell hybrids (MCHs) during tumor growth in SCID mice. In an attempt to narrow down the eliminated region, we have studied 22 new SCID mouse tumors derived from 5 MCH lines carrying human chr3. They were analyzed by fluorescence in situ hybridization (FISH), Southern blotting, and polymerase chain reaction (PCR). MCHs that carried human chr1, chr8, chr13, and chr17 were examined as controls. We could identify a common eliminated region (CER) at 3p21.3, bordered distally by D3S1260 and proximally by D3S643/D3F15S2. Eight of 53 chr3-specific PCR markers, AP20R, D3S966, D3S3559, D3S1029, WI-7947, D3S2354, AFMb362wb9, and D3S32. were localized within the CER. This finding is consistent with the notion that a tumor suppressor gene may be located in this area, as suggested by frequent loss of heterozygosity (LOH) within this region observed in several types of solid tumors.
我们之前已经表明,在SCID小鼠体内肿瘤生长过程中,跨越3p24 - p21.3区域的四个标记物THRB、AP20R、D3S1029和D3S32,会从三个人类3号染色体(chr3)/小鼠微细胞杂种(MCH)中定期消除。为了缩小消除区域,我们研究了来自携带人类chr3的5个MCH系的22个新的SCID小鼠肿瘤。通过荧光原位杂交(FISH)、Southern印迹和聚合酶链反应(PCR)对它们进行了分析。携带人类chr1、chr8、chr13和chr17的MCH作为对照进行检测。我们能够在3p21.3处确定一个共同消除区域(CER),其远端以D3S1260为界,近端以D3S643/D3F15S2为界。53个chr3特异性PCR标记物中的8个,即AP20R、D3S966、D3S3559、D3S1029、WI - 7947、D3S2354、AFMb362wb9和D3S32,定位于CER内。这一发现与肿瘤抑制基因可能位于该区域的观点一致,正如在几种实体瘤中该区域频繁出现杂合性缺失(LOH)所表明的那样。