2014-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/650575摘要：平滑肌肉瘤為相對少見的軟組織肉瘤的一種，除了子宮之外也可發生於表淺、深部軟組織、血管或皮膚。目前對於平滑肌肉瘤的致病機轉所知十分有限，其細胞遺傳學及基因變化相當複雜而缺乏獨特的分子病理標記。平滑肌肉瘤病人的預後較差且目前沒有針對此腫瘤有效的標靶治療，因此有必要針對此種腫瘤做更進一步的研究以了解其致病機轉並改善治療成績。 端粒的縮短為細胞分裂時的必然現象而端粒縮短到一定程度後細胞會無法繼續分裂或死亡，而腫瘤要無限制地生長必須要克服此一限制。目前已知克服端粒縮短的機制主要有兩種: 一為端粒酶反轉錄酶基因(TERT)的啟動子突變，這些突變會增加端粒酶的表現；另一則是替代性端粒延長機制，在某些腫瘤此機制是由 ATRX 或 DAXX 失去表現導致，ATRX 及 DAXX 的表現可用免疫組織化學染色來檢測，而替代性端粒延長現象則可用端粒的螢光原位雜交證實。 我們已收集超過 100 例的平滑肌肉瘤，在這個計畫裡，我們想針對這種腫瘤進行端粒酶反轉錄酶的啟動子突變、ATRX/DAXX 免疫組織化學染色及端粒的螢光原位雜交研究等以了解此種腫瘤維持端粒長度的機制。這些分子病理標記可和臨床病理特性做更進一步的分析，並且可能有助於將來發展更有效的治療。 <br> Abstract: Leiomyosarcoma is a relatively uncommon soft tissue sarcoma. It occurs in uterus and extra-uterine sites, such as deep and superficial soft tissues, blood vessels and skin. The pathogenesis of leiomyosarcoma is poorly-understood. Its cytogenetics and genetic alterations are highly complex and lacks unique molecular pathogenic markers. The prognosis of patients with leiomyosarcoma is poorer and there is no effective targeting therapy currently. Thus further studies are necessary to better appreciate its pathogenesis and improve clinical treatment result. Telomere shortening is an inevitable phenomenon during mitosis. Critical telomere shortening leads to cease of cell division or cell death. Tumor cells must overcome this limitation to become immortal. Currently there are two major mechanisms for telomere length maintenance; one is the mutations in the promoter of the TERT gene, which encodes the reverse transcriptase subunit of telomerase. The mutations lead to increased transcription and expression of telomerase. The other is the alternative lengthening of telomere, which in some tumors is caused by loss of expression of either ATRX or DAXX. The expression of ATRX or DAXX can be studied by immunohistochemical stain. The phenomenon of alternative lengthening of telomere can be confirmed by telomere-specific fluorescence in situ hybridization. We have collected more than 100 cases of leiomyosarcoma. In this proposal, we want to perform TERT promoter mutation analysis, ATRX/DAXX immunohistochemical stain, telomere-specific fluorescence in situ hybridization, etc to better appreciate the mechanism of telomere maintenance in this tumor. These molecular pathogenic markers can be further analyzed with clinical and pathological features and may contribute to the development of more effective therapy in the future.平滑肌肉瘤端粒酶端粒螢光原位雜交leiomyosarcomatelomerasetelomerefluorescence in situ hybridization