Saito S, Sirahama S, Matsushima M, Suzuki M, Sagae S, Kudo R, Saito J, Noda K, Nakamura Y
SRL, Inc., Hachioji, Tokyo, Japan.
Cancer Res. 1996 Dec 15;56(24):5586-9.
Allelic deletions of chromosome 6q that occur frequently in ovarian cancers imply the presence of a putative tumor suppressor gene in this chromosomal vicinity. We analyzed DNA from 32 patients with ovarian carcinomas for loss of heterozygosity at loci on the distal portion of chromosome 6q and constructed a detailed deletion map. The map indicated a commonly deleted region between loci D6S149 (defined by CI6-24) and A2, which are estimated to be 300 kb apart on the basis of our cosmid contig map. By means of exon trapping, we found that the human AF-6 gene, which is disrupted in acute myeloid leukemia cells that carry a (6;11)(q27;q23) translocation, is located within the commonly deleted region. Subsequent screening of the AF-6 gene in ovarian carcinomas revealed no mutations. However, our mapping results, which narrowed the region containing the putative tumor suppressor gene to a 300-kb segment of 6q27, will facilitate further efforts to identify a gene associated with ovarian cancer.
6号染色体长臂(6q)的等位基因缺失在卵巢癌中频繁出现,这意味着在该染色体区域附近存在一个假定的肿瘤抑制基因。我们分析了32例卵巢癌患者的DNA,以检测6q远端位点的杂合性缺失,并构建了详细的缺失图谱。该图谱显示,在D6S149(由CI6 - 24定义)和A2位点之间存在一个常见的缺失区域,根据我们的黏粒重叠群图谱估计,这两个位点相距300 kb。通过外显子捕获,我们发现人类AF - 6基因位于这个常见的缺失区域内,该基因在携带(6;11)(q27;q23)易位的急性髓系白血病细胞中发生了破坏。随后对卵巢癌中AF - 6基因的筛查未发现突变。然而,我们的定位结果将包含假定肿瘤抑制基因的区域缩小到6q27的一个300 kb片段,这将有助于进一步努力鉴定与卵巢癌相关的基因。