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放射線引起的惡性纖維組織細胞瘤在第三和第十一對染色體之異合性喪失-病例報告

Loss of Heterozygosity on Chromosomes 3 and 11 in a Radiation-Induced Malignant Fibrous Histiocytoma – Case Report

摘要


癌症的形成大都是一連串的基因變化所致,其中抑癌基因的不活化是癌細胞形成最常見的現象,雖然抑癌基因的不活化有很多機轉,找出腫瘤細胞失去的染色體片段,再從中找尋可能含有的抑癌基因是一種有效的方法。來自雙親的兩個同源染色體,若其中之一有一段缺失,謂之有失異合性。部份頭頸部癌症在第3,9,11對染色體已被發現有失異合性。頭頸部區域之放射線引起的惡性纖維組織細胞瘤,是一種惡性度極高的肉瘤,和原發性的鎮一樣,前者非常罕見但生長極為快速,復發率高。為瞭解放射線引起的惡性纖維組織細胞瘤在第3,9,11對染色體有無失異合性的情形,取1名惡性纖維組織細胞癌病人的癌組織,及抽取周邊血液,分別萃取癌細胞及正常淋巴球之去氧核榶醣核酸,然後以位於第3,9,11對染色體上特定位置的53個附有螢光物質的微衛星多形標記引子,放入分別含有正常細胞或癌細胞去氧核醣核酸的反應液中,藉助聚合酵素鏈反應複製60次,確定有產物後,便在Perkin-Elmer/Applied Biosystems(PE/ABI)的377去氧核醣核酸分析儀進行電泳,經雷射激發,蒐集訊息於電腦,再以GeneScanTM軟體判讀。結果在染色體3p的D3S1300和3q的D3S1262、D3S1311及染色體11p的D11S922有失異合性的情形。

並列摘要


Malignant transformation in tumor development results from a series of genetic changes and the inactivation of tumor suppressor genes is among the most common molecular events that contribute to tumorigenesis. Although a variety of mechanisms exsist for the inactivation of tumor suppressor genes, loss of chromosomal segments in tumor cells has proven common and useful in mapping regions containing putative tumor suppressor genes. Loss of one homologous chromosomal segment means loss of heterozygosity (LOH) (hemizygous deletion). Microsatellite polymorphic markers consist of CA dinucleotide repeats and often display extensive length polymorphism. LOH on the chromosomes 3, 9, 11 by means of microsatellite markers has been found in squamous cell carcinomas of the head and neck. The radiation-induced malignant fibrous histiocytoma in the head and neck region is rare and grows very rapidly with a poor prognosis. To detect LOH in this cancer, we analysed microsatellite polymorphism in the tumor tissue and peripheral lymphocytes of a patient with radiation-induced malignant fibrous histiocytoma. Fifty-three microsatellite polymorphic markers with corresponding pairs of primers labeled with fluorescent on chromosomes 3, 9 and 11 were used. The respective DNA’s of the cancer cells and normal lymphocytes were amplified with polymerase chain reaction (PCR). We analysed the PCR products on a Model 377 DNA Analysis System (Perkin-Elmer/Applied Biosystems Division) using the GeneScanTM software. LOH was found on one marker of chromosome arm 3p (D3S1300), two markers of chromosome arm 3q (D3S1262, D3S1311), and one marker of chromosome arm 11p (D11S922).

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