論文名稱:

口腔鱗狀上皮細胞癌之抑癌基因異常

 

Alterations of tumor suppressor gene in oral squamous cell carcinoma

研究生:

曾泳盛  Yeong-Sheng Tzeng

 

(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

          學年度:

85

          語文別:

中文

          出版年:

86

關鍵字:

牙醫  DENTIST

 

牙醫學  DENTISTRY

 

口腔  ORAL-HEALTH

 

鱗狀上皮細胞 

        論文頁數:

73

摘要:

國外有頭頸部、口腔癌之p16/MTS1抑癌基因突變以及刪除的研究,但到目前為止,還未有人針對口腔癌做過度甲基化為上基因層級之變化的研究。本研究發現在我們國人口腔鱗狀上皮細胞癌中有6.3%(7/110)之突變率,其中有胺基酸置換突變、終止訊號之產生、複製性刪除以及表現子及插入子疊接區之突變;與正常口腔組織對照,不具同質性接合子或異質,性接合子刪除;18%(10/55)之檢體具有表現子1內之過度甲基化;與國外相較突變率及刪除率都接近。本研究之病患65%有嚼食檳榔及抽煙的習慣,跟國外之研究資料比較起來,嚼食檳榔的危險因子似未加重p16/MTS1基因之變異。本研究之檢體分成只抽煙、既抽煙又嚼食檳榔以及不吃檳榔不抽煙三個子族群,p16/MTS1突變率在此三子群並無統計上差異(P=0.22),顯示p16/MTS1之基因突變可能和已知之危險因子無關。本研究亦發現p53 APCMCC抑癌基因在國人口腔癌之刪除率亦不高(3%ll%),而Rb-1之刪除不可見。顯示這幾個抑癌基因之刪除性失活對國人口腔鱗狀上皮細胞癌之生成角色並不太重要。與以往吾人之研究綜合分析知不同之抑癌基因失活參與了口腔癌之生成,而p53之突變發生率為26%,在國人口腔癌扮演最顯著的角色。

   
 

Mutations and deletion of pl6/MTS1 tumor suppressor gene (TSG) have been studied in Head and Neck cancers as well as oral squamous cell carcinomas (OSCCs) in territories at where tobacco smoking is the principle risk factor. However, there were no report whether hypermethylation (epigenetic phenomenon) corresponds to mactivation of pl6/MTS1 in OSCCs. The current study identified p16/MTS1 gene mutations in 6.3% (7/110) of OSCCs in Taiwan. Five mutations were in exon 2 that consists of amino residues substitution, stop codon formation, and duplicative deletion. Two mutations occurred at intron l/exon 2 junction that cause alternative splicing  and truncation of pl6/MTS1 protein. No homozygous deletion or loss of heterozygosity (LOH) was identified by comparative analysis using non-diseased paring tissue as control. Eighteen percent (10/55) of the specimen exhibited hypermethylation in CpG islands of exon 1. Patients who consumed both betel quid (BQ) and tobacco represented a major portion (65%) of our  study population. It appears unlikely that BQ perturbates the incidence of pl6/MTS1 gene alterations in OSCCs when comparing our data with previous reports. When dividing our objects into smoker, BQ-user/smoker and non-BQ-user/nonsmoker subgroups, no statistical difference(P=0.22) was found on the incidence of mutation among these subgroups that suggested a lack of correlation between p16/MTS1 alterations and known risk factors. LOH analyses conducted on putative TSGs show an infrequent involvement of p53 (6%), APC (11%) and MCC (3%) during oral carcinogenesis, whereas no LOH of Rb-1 was identifiable. This study and our previous findings indicated that multiple TSGs alterations are present in oral cancers, p53 mutation tends to be more prevalent (26%) than otherwise been investigated.