Deletion Mapping of Chromosomes in Malignant Lymphoma and Molecular Cloning of a Putative Novel Tumor Suppressor Gene from the Loci

等位基因缺失被认为是肿瘤抑制基因（TSG）存在的指标。利用分布在所有常染色体上的39个高信息量微卫星标记进行等位基因型研究，发现B细胞非霍奇金淋巴瘤6 p处存在频繁的杂合性丢失（洛）。为了确定共同的缺失区（CDR），我们进行了精细的缺失定位，使用26个高度多态性的微卫星标记6p。最常见的洛缺失发生在D 6S 1721，其中18例提供信息的病例中有9例（50%）有等位基因丢失。32例中有17例（53%）在6 p上至少有一个位点存在洛缺失。其中10例间质缺失，其洛合性丢失（LOH）模式显示两个位于6 p的CDR，一个位于D 6S 1721和D 6S 260之间（6p 23 -24），另一个位于D 6S 265和D 6S 291之间（6p 21）。CDKN 1A（p21）基因位于6p 21的CDR区间内，但在32例患者中均未发现该基因突变。这些数据表明，这两个位点可能窝藏新的假定的TSGs负责恶性淋巴瘤的发病机制。我们已经构建了酵母人工染色体（YAC）克隆的重叠群，其跨越6p 23 -24处最常见的CDR。该YAC重叠群可用于该区域的精细物理定位和候选TSG的克隆。

Allelic deletions have been thought to be indicators of the presence of tumor suppressor genes (TSGs). As indicated by this allelotype study using 39 highly informative microsatellite markers distributed among all autosomal chromosomes, frequent loss of heterozygosity (LOH) has been found at 6p in B-cell non-Hodgkin lymphoma. To identify the common deleted regions (CDRs), we performed fine deletion mapping using 26 highly polymorphic microsatellite markers on 6p. The most frequent LOH occurred at D6S1721, where 9 of 18 of the informative cases (50%) had allelic losses. Seventeen of 32 cases (53%) exhibited LOH at least at one locus on 6p. Ten of these 17 cases showed interstitial deletions, and their LOH patterns indicated two CDRs on 6p ; one between D6S1721 and D6S260 (at 6p23-24), the other between D6S265 and D6S291 (at 6p21). The genetic distance of both CDRs was 6 cM.The CDKN1A (p21) is reported to be located within the interval of the CDR at 6p21, but no mutation of the gene was found in these 32 patients. These data suggested that these two loci might harbor novel putative TSGs responsible for the pathogenesis of malignant lymphoma. We have constructed a contig of yeast artificial chromosome (YAC) clones spanning the most frequent CDR at 6p23-24. This YAC contig can be used for fine physical mapping of the region and cloning of the candidate TSGs.