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

几种癌基因和肿瘤抑制基因，包括c-myc、c-erbB2/HER2/neu、K-ras、p53、Rb、PTEN和BRCA1基因在人类卵巢癌中发生遗传改变。p53基因突变的发生率为30-80%，然而，其他基因的遗传改变仅在一小部分卵巢癌中被检测到。卵巢肿瘤抑制基因的鉴定对卵巢癌发生机制的阐明和卵巢癌基因治疗的发展具有重要意义。为了确定候选的卵巢肿瘤抑制基因位点，我们使用散发性卵巢癌患者的微解剖DNA对等位基因丢失区域进行了全基因组扫描。在获得知情同意书后，对肿瘤和非肿瘤细胞进行激光捕获微解剖（LCM），并从这些细胞中提取基因组DNA。对来自98例卵巢癌和相应正常组织的DNA进行了分析，以检测覆盖所有22条常染色体的218个多态性标记的微卫星改变。在本研究中，17p染色体上的LOH发生率最高（74%）。此外，在染色体5q、5p、8p、13q、14q、14q、17q、18q和22q上观察到频繁的缺失（bbb50 %）。现在我们绘制了人类卵巢癌的缺失图谱并在这些染色体臂上寻找卵巢癌细胞系的纯合缺失。

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.