論文名稱:

染色體 11q13 重要致癌基因增幅在口腔鱗狀上皮細胞癌及其高危險族群之探討

 

Copy Number Amplification of 11q13 Oncogene in Oral Squamous Cell Carcinoma and Oral Brushed Samples from Areca Chewer

研究生:

羅尹伸  Yin-Shen Lo

 

(以作者名查詢陽明大學館藏系統)

 

(以作者名查詢全國圖書書目資訊網)

指導教授:

張國威  Kuo-Wei Chang

        學位類別:

碩士

        學校名稱:

國立陽明大學

系所名稱:

口腔生物研究所

            學號:

39217004

          學年度:

93

          語文別:

中文

          出版年:

94

關鍵字:

口腔鱗狀上皮癌  Oral Squamous Cell Carcinoma

 

染色體  11q13

 

  Oncogene

 

  Q-PCR

全文說明:

電子全文

        論文頁數:

72

摘要:

台灣地區近年口腔癌的死亡率及發生率不斷的上升,與嚼食檳榔有密切關係。近來醫療雖有長足進步,但口腔鱗狀上皮細胞癌(OSCC)的存活率卻仍未見改善。因此 OSCC 的診斷及癌化機轉的了解有其迫切性。先前實驗室發現 11q13 上之致癌基因增幅極高。11q13致癌基因的改變在各癌症都相當重要,本研究意圖在口腔癌發展的早期也能發現相同的增幅,藉以推測這些基因對口腔癌之癌化機轉之重要性及作早期診斷。

 

    本研究以即時定量聚合酶分析染色體 11q13 上之 CCND1EMS1PAK1 重要致癌基因在 OSCC 細胞株及 55例組織的基因套數異常。結果顯示CCND1EMS1PAK1 OSCC 中有基因套數異常增幅之情形,分別為 38%62% 71%。在蛋白質表現上,利用免疫組織染色法分析 PAK1 蛋白在 41 OSCC 16 組非癌配對組織(NCMT) OSCC 之表現情形。發現 PAK1蛋白表現在 OSCC 大多為強陽性,明顯高於 NCMT。分析 11q13 重要致癌基因在 40 例高危險族群 (長年嚼食檳榔者而經醫師檢驗未發現病變之人們) 其口腔黏膜抹片之基因套數的變化,發現各基因之增幅在 OSCC 高危險族群可偵測到,且有高達 50% 的人至少有一個 11q13 重要致癌基因之增幅。

 

    本研究中發現在 OSCC 發展過程中11q13 致癌基因之顯著增幅異常,支持這些基因對於 OSCC 的生成有重要之影響;PAK1 PI3K 信號傳遞系統重要元件,PAK1 基因異常增幅至目前為止首次在OSCC 中發現,而這些 11q13 致癌基因增幅異常之發現可望作為早期 OSCC 篩檢之標誌。

   
 

The incidence and mortality rate of oral squamous cell carcinoma (OSCC) was continuously ascending in Taiwan in the past years due to the abuse in areca chewing. Although surgical approaches and other medical regimens have progressed remarkably recently, the survival rate of OSCC has not significantly improved. Thereby, early diagnosis to assure early treatment and mechanistic understanding of oral carcinogenesis are crucial for OSCC resolution. Previously, high level of 11q13 amplification in OSCC has been identified in our laboratory. Oncogenes located at 11q13 seem important for carcinogenesis of various cancers. This study attempted to identify the 11q13oncogenomic amplification in oral carcinogenesis, to highlight their mechanistic importance and to validate early diagnosis.

 

Real-time quantitative PCR (Q-PCR) was used to assay the copy number of 11q13 oncogenes CCND1, EMS1 and PAK1 in 55 OSCC cases. The results indicated that CCND1, EMS1 and PAK1 were amplified in 38%, 62% and 71% OSCC, respectively. Immunohistochemistry analysis performed on 41 OSCC and 16 non-cancerous match tissues (NCMTs) revealed that nearly all OSCC had strong PAK immunoreactivity, which was considerably higher than NCMT. We further extended our Q-PCR analysis to evaluate the copy number of 11q13 oncogenes in brushed oral cells from 40 areca chewers, who are in high risk for OSCC. Q-PCR can detect oncogenomic amplification in this cohort. Moreover, 50% cases exhibited amplification of at least one oncogene.

 

The findings of frequent 11q13 oncogenomic amplification in OSCC substantiated the contributive roles of CCND1, EMS1 and PAK1 for oral carcinogenesis. PAK is an important element involving in PI3K pathway. This study is the first to demonstrate PAK1 alterations in OSCC. 11q13 oncogenomic amplification could be a potential marker for gene alterations in early oral carcinogenesis.