Establishment of criteria and technique for molecular genetical diagnosis of urothelial cancer

尿路上皮癌分子遗传学诊断标准和技术的建立

• 批准号: 06454457
• 负责人: YOSHIDA Osamu
• 金额: $ 3.97万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454457/
• 关键词: Urothelial cancer; Genetic alteration; Urine cytology; p53; p16; MTS1, MTS2; MDR1, MRP; Primary culture; MASA; MTS1,MTS2; MDR1,MRP; 分子遺伝学的診断; 尿中剥離細胞培養; p53遺伝子異常; MDM2遺伝子増幅; MTSL; p16遺伝子異常; 多剤耐性関連遺伝子発現

We have reported the losses of heterozygosity on chromosome 9 and 17 are clinically important and now we try to examine several molecular markers to apply for molecular genetic diagnosis.P53 is known as a target gene of loss of heterozygosity of chromosome 17 and the mutation of it is in relation to pathological features. This study has proved p53 mutation may be a clinical marker to predict whether the urothelial cancer will progress to be an invasive cancer and has no relation with radiosensitivity.MTS1 and MTS2, those are located on chromosome 9, are tumor supressor genes. This study has proved homozygous deletion or point mutation of these genes often occured in urothelial cancers but has not obvious relation with clinical features which must be proved with further study.Otherwise decrease of E-cadherin, which is one of adhesion molecule expressed in urothelium, is often observed and is in relation to clinical and pathological features.Multiple drug resistance genes such as MDR1, MRP,topo II and GST-pai are clinically important because they are considered to have a relation with drug sensitivity, but no abnormal expression is observed in urothelial cancers.And then we try to develop molecular genetic technique for diagnosis using p53 as a molecular marker.1st, we have modified MASA,that is mutant allele-specific amplification, to avoid false positive and have suceeded to detect cancer cell in urine sediment. And next using short term culture of urine sediment, this study has proved immunocytochemical staining can detect p53 mutation of primary tumor. This may be a powerful method to know malignancy of urothelial cancer.

P53是17号染色体杂合性缺失的靶基因，其突变与病理特征有关。本研究证实p53突变可能是预测尿路上皮癌是否向浸润性癌发展的一个临床指标，与放射敏感性无关;位于9号染色体上的MTS 1和MTS 2是抑癌基因。本研究证实这些基因的纯合性缺失或点突变常发生在尿路上皮癌中，但与临床特征关系不明显，有待进一步研究证实;另外，作为粘附分子之一的E-cadherin在尿路上皮癌中表达减少，与临床和病理特征有关;多药耐药基因如MDR 1、MRP、Topo Ⅱ和GST-pai被认为与药物敏感性有关，在临床上具有重要意义，但在尿路上皮癌中未发现异常表达，因此我们尝试以p53为分子标记，发展分子遗传学诊断技术。避免了假阳性的发生，有利于检测尿沉渣中的癌细胞。其次，本研究通过尿沉渣短期培养，证实免疫细胞化学染色可以检测原发肿瘤p53突变。这可能是了解尿路上皮癌恶性程度的有力手段。

项目成果

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