Pulido H A, Fakruddin M J, Chatterjee A, Esplin E D, Beleño N, Martinez G, Posso H, Evans G A, Murty V V
Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Cancer Res. 2000 Dec 1;60(23):6677-82.
Previous functional and deletion mapping studies on cervical cancer (CC) have implicated one or more tumor suppressor genes (TSGs) on chromosome 11 at q13 and q22-24 regions. Of these, the 11q22-24 region exhibits frequent allelic deletions in a variety of solid tumor types, suggesting the presence of critical genes for tumor suppression in this region. However, the precise region of deletion on 11q is not clearly defined in CC. In an attempt to accurately map the deleted region, we performed an extensive loss of heterozygosity (LOH) mapping in 58 tumors using 25 polymorphic loci on both the short and long arms. The pattern of LOH identified three sites of deletions, two on 11p (p15.11-p15.3 and p12-13), and one on 11q (q23.1-q23.2). The 11q23.1-q23.2 exhibited highest frequency (60.6%) of deletions, suggesting that this could be the site of a candidate TSG in CC. The minimal deletion at 11q23.1-23.2 was restricted to a 6-cM region between 123.5 and 129.5 cM genetic distance on chromosome 11, identifying the site of a potential TSG important in the pathogenesis of CC. At least five known genes and 28 UniGene clusters were mapped to the present commonly deleted region. In addition, we have excluded a previously known TSG PPP2R1B at 11q23 as a deletion target in CC. The definition of the minimal deletion and the availability of expressed sequence resources should facilitate the identification of the candidate TSG.
先前针对宫颈癌（CC）的功能和缺失定位研究表明，11号染色体q13和q22 - 24区域存在一个或多个肿瘤抑制基因（TSG）。其中，11q22 - 24区域在多种实体瘤类型中频繁出现等位基因缺失，提示该区域存在关键的肿瘤抑制基因。然而，CC中11q上的精确缺失区域尚未明确界定。为了准确绘制缺失区域，我们使用短臂和长臂上的25个多态性位点，对58个肿瘤进行了广泛的杂合性缺失（LOH）定位。LOH模式确定了三个缺失位点，两个在11p（p15.11 - p15.3和p12 - 13），一个在11q（q23.1 - q23.2）。11q23.1 - q23.2的缺失频率最高（60.6%），表明这可能是CC中候选TSG的位点。11q23.1 - 23.2的最小缺失区域局限于11号染色体上123.5至129.5 cM遗传距离之间的6 - cM区域，确定了一个在CC发病机制中起重要作用的潜在TSG位点。至少五个已知基因和28个单基因簇被定位到当前的常见缺失区域。此外，我们已排除11q23处先前已知的TSG PPP2R1B作为CC中的缺失靶点。最小缺失区域的定义和表达序列资源的可用性应有助于候选TSG的鉴定。
