- 學位論文
胃黏膜相關淋巴組織淋巴癌之基因表現探討
Genomic investigation of gastric mucosa-associated lymphoid tissue lymphoma
摘要
研究背景：胃黏膜相關淋巴組織 (Mucosa-Associated Lymphoid Tissue，MALT)淋巴癌的發生與幽門螺旋桿菌 (Helicobacter pylori；H.P.) 的感染有高度相關。根據使用抗生素的結果，可以將胃黏膜相關淋巴組織淋巴癌分成幽門螺旋桿菌依賴性 (H.P.-dependent)胃黏膜相關淋巴組織淋巴癌與幽門螺旋桿菌非依賴性 (H.P.-independent)胃黏膜相關淋巴組織淋巴癌兩種。研究動機：雖然t(11;18)(q21;q21)的易位為幽門螺旋桿菌非依賴性胃黏膜相關淋巴組織淋巴癌的預測指標之一，但是卻很少在腫瘤分期IE時期出現。因此，尋找另一個預測指標能及早檢測出幽門螺旋桿菌非依賴性胃黏膜相關淋巴組織淋巴癌是需要的。在本實驗中，我們假設在IE時期的幽門螺旋桿菌依賴性 (H.P.-dependent)與幽門螺旋桿菌非依賴性 (H.P.-independent)胃黏膜相關淋巴組織淋巴癌中有不同的基因表現存在。方法：利用微陣列競爭型基因體雜合技術 (Array comparative genomic hybridization，array CGH) 與單一核苷酸多樣性 (Single nucleotide polymorphism，SNP) 微陣列研究IE時期的幽門螺旋桿菌依賴性與幽門螺旋桿菌非依賴性胃黏膜相關淋巴組織淋巴癌中不同的基因表現，接著以螢光原位雜合技術 (Fluorescence in situ hybridization，FISH ) 探討核轉錄因子 (Nuclear Factor-KappaB，NF-κB)傳導路徑相關基因之變異，並以即時定量聚合酶鏈鎖反應 (Quantitative real time polymerase chain reaction Q-PCR)進一步偵測基因BCL2 mRNA的表現量。結果與結論：IE時期的幽門螺旋桿菌依賴性與幽門螺旋桿菌非依賴性胃黏膜相關淋巴組織淋巴癌中存在不同的基因表現模式，尤其是BCL2不同的缺失區域可能作為一指標分辨兩種類型的胃黏膜相關淋巴組織淋巴癌。此外，TNFAIP3的缺失可能作為幽門螺旋桿菌依賴性胃黏膜相關淋巴組織淋巴癌的生物標記。而CARD9或TRAF2的易位也可能在胃黏膜相關淋巴組織淋巴癌的腫瘤形成中扮演重要的角色，但我們仍需更大的樣本數加以證實其論點。
並列摘要
Background: The infection of Helicobacter pylori (H.P.) is highly associated with the development of gastric MALT lymphoma. According to the response of antibiotics treatment, it can be divided in to two groups, H.P.- dependent and - independent. Motivation: Although the t(11;18)(q21;q21) translocation is one of the possible predict markers for H.P.- independent MALT lymphoma, but rare in MALT lymphoma on IE stage. Therefore, another useful marker is needed for early detection of this disease. Here we hypothesize that there are different genetic profiling exist in H.P.-dependent and H.P.-independent gastric MALT lymphoma on IE stage. Methods: We performed array comparative genomic hybridization (array CGH) and single nucleotide polymorphism array (SNP array) to reveal the genetic profiles and further distinct two subgroups of H.P.-dependent and -independent gastric MALT lymphoma on IE stage. Then we further focus on NF-κB related genes by using fluorescence in situ hybridization analysis (FISH). In addition, to confirm the results of FISH, we use quantitative real time polymerase chain reaction (Q-PCR) to detect the mRNA expression of BCL2. Results and conclusion: The genomic patterns presented exact different types of information between the two subtypes of H.P.-independent and -dependent in gastric MALT lymphoma on IE stage. Especially, the different deletion regions of BCL2 in both tumor types can be considered as a useful predictor to distinct both subtypes. Moreover, loss of TNFAIP3 might be as a specific biomarker of H.P.-dependent gastric MALT lymphoma on IE stage. Further, either the translocation of CARD9 or TRAF2 could also play a role in MALT lymphoma tumorigenesis.