Search for candidate ovarian tumor suppressor gene loci from a genomewide scan of ovarian cancers

在人类卵巢癌中，包括c-myc、c-erbB 2/HER 2/neu、K-ras、p53、Rb、PTEN和BRCA 1基因在内的几种癌基因和肿瘤抑制基因发生了遗传改变。p53基因突变的发生率为30- 80%，而其他基因的突变仅在一小部分卵巢癌中发现。卵巢肿瘤抑制基因的鉴定对阐明卵巢癌的发生机制和卵巢癌的基因治疗具有重要意义。为了确定候选的卵巢肿瘤抑制基因位点，我们使用来自散发性卵巢癌患者的微切割DNA进行全基因组扫描以寻找等位基因丢失区域。在获得签署的知情同意书后，对肿瘤和非肿瘤细胞进行激光捕获微切割（LCM），并从这些细胞中提取基因组DNA。对98例卵巢癌及相应正常组织的22条常染色体218个微卫星多态性标记进行了分析，发现17号染色体上的洛缺失频率最高（74%）。此外，在染色体5 q、5 p、8 p、13 q、14 q、14 q、17 q、18 q和22 q上也观察到了频繁的缺失（>50%）。

Several oncogenes and tumor suppressor genes including c-myc, c-erbB2/HER2/neu, K-ras, p53, Rb, PTEN, and BRCA1 genes are genetically altered in human ovarian cancers. Mutations of p53 gene have been detected with the incidence of 30-80%, however, genetic alterations in the other genes have been detected only in a small fraction of ovarian cancer. Identification of ovarian tumor suppressor gene is important for elucidation of ovarian cartinogenesis and development of gene therapy for ovarian cancer. To identify candidate ovarian tumor suppressor gene loci, we conducted a genomewide scan for regions of allelic loss using microdissected DNA from sporadic ovarian cancer patients.After signed informed consent was obtained, tumor and nontumor cells were laser capture microdissected (LCM) and genomic DNA was extracted from these cells. DNA from 98 ovarian cancers and corresponding normal tissue was analyzed for microsatellite alterations in 218 polymorphic markers covering all 22 autosomal chromosomes.In this study, the highest frequency of LOH on chromosome 17p was observed (74%). In addition, frequent losses (>50%) were observed on chromosome 5q, 5p, 8p, 13q, 14q, 14q, 17q, 18q, and 22q.Now we make the deletion map which is detail in human ovarian cancers and search for homozygous deletion in ovarian cancer cell lines on these chromosome arms.