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（TSGs）存在的指标。这项利用分布在所有常染色体中的39个信息丰富的微卫星标记进行的等位型研究表明，在b细胞非霍奇金淋巴瘤的6p处发现了频繁的杂合性缺失（LOH）。为了确定共同缺失区域（cdr），我们利用6p上26个高度多态性的微卫星标记进行了精细的缺失定位。最常见的LOH发生在D6S1721, 18例信息病例中有9例（50%）有等位基因丢失。32例中有17例（53%）在6p至少有一个位点出现LOH。17例中有10例出现间质缺失，其LOH模式显示6p有2个cdr；一个在D6S1721和D6S260之间（6p23-24），另一个在D6S265和D6S291之间（6p21）。两个cdr的遗传距离均为6 cM。据报道，CDKN1A （p21）位于CDR的6p21区间内，但在这32例患者中未发现该基因突变。这些数据表明，这两个基因座可能含有新的假定的tsg，负责恶性淋巴瘤的发病机制。我们构建了酵母人工染色体（YAC）克隆组，这些克隆跨越了最常见的CDR位点6p23-24。该YAC配置可用于该区域的精细物理映射和候选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.