中华内分泌代谢杂志
中華內分泌代謝雜誌
중화내분비대사잡지
CHINESE JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2010年
11期
954-958
,共5页
付春莉%曾正陪%李汉忠%童安莉%卢琳%陈适%王永慧%李新萍%张妲%杨薇%李明%宋爱羚
付春莉%曾正陪%李漢忠%童安莉%盧琳%陳適%王永慧%李新萍%張妲%楊薇%李明%宋愛羚
부춘리%증정배%리한충%동안리%로림%진괄%왕영혜%리신평%장달%양미%리명%송애령
p16基因%甲基化%嗜铬细胞瘤%基因突变%基因表达
p16基因%甲基化%嗜鉻細胞瘤%基因突變%基因錶達
p16기인%갑기화%기락세포류%기인돌변%기인표체
p16 gene%Methylation%Pheochromocytoma%Gene mutation%Gene expression
目的 检测嗜铬细胞瘤(PHEO)和副神经节瘤(PGL)中p16基因突变和启动子区DNA甲基化改变,分析其与患者临床特征之间的关系.方法收集34例(PHEO 20例、PGL14例)组织标本及患者临床资料,通过甲基化特异性PCR(MSP)测定p16基因启动子区甲基化状态,DNA测序检测基因序列以及RT-PCR方法测定其mRNA表达.结果 (1)34例肿瘤组织中未发现p16基因纯合缺失及点突变;(2)35.3%(12/34)的患者存在p16基因高甲基化,p16基因甲基化阳性标本中,PHEO和PGL分别占25%和75%,两者差异有统计学意义(P=0.005);p16基因甲基化在恶性、单发肿瘤、发病年龄早的亚组中有增高趋势(P＞0.05);(3)甲基化与非甲基化肿瘤组织之间p16 mRNA表达无统计学差异;不同特点的肿瘤中其mRNA表达亦无统计学差异,但恶性肿瘤p16 mRNA表达与良性肿瘤相比有下降的趋势(0.83±0.65对1.12±0.81,P=0.278).结论人PHEO和PGL中,p16基因纯合缺失和突变并不常见,但p16基因启动子区甲基化是其失活的主要形式.
目的 檢測嗜鉻細胞瘤(PHEO)和副神經節瘤(PGL)中p16基因突變和啟動子區DNA甲基化改變,分析其與患者臨床特徵之間的關繫.方法收集34例(PHEO 20例、PGL14例)組織標本及患者臨床資料,通過甲基化特異性PCR(MSP)測定p16基因啟動子區甲基化狀態,DNA測序檢測基因序列以及RT-PCR方法測定其mRNA錶達.結果 (1)34例腫瘤組織中未髮現p16基因純閤缺失及點突變;(2)35.3%(12/34)的患者存在p16基因高甲基化,p16基因甲基化暘性標本中,PHEO和PGL分彆佔25%和75%,兩者差異有統計學意義(P=0.005);p16基因甲基化在噁性、單髮腫瘤、髮病年齡早的亞組中有增高趨勢(P＞0.05);(3)甲基化與非甲基化腫瘤組織之間p16 mRNA錶達無統計學差異;不同特點的腫瘤中其mRNA錶達亦無統計學差異,但噁性腫瘤p16 mRNA錶達與良性腫瘤相比有下降的趨勢(0.83±0.65對1.12±0.81,P=0.278).結論人PHEO和PGL中,p16基因純閤缺失和突變併不常見,但p16基因啟動子區甲基化是其失活的主要形式.
목적 검측기락세포류(PHEO)화부신경절류(PGL)중p16기인돌변화계동자구DNA갑기화개변,분석기여환자림상특정지간적관계.방법수집34례(PHEO 20례、PGL14례)조직표본급환자림상자료,통과갑기화특이성PCR(MSP)측정p16기인계동자구갑기화상태,DNA측서검측기인서렬이급RT-PCR방법측정기mRNA표체.결과 (1)34례종류조직중미발현p16기인순합결실급점돌변;(2)35.3%(12/34)적환자존재p16기인고갑기화,p16기인갑기화양성표본중,PHEO화PGL분별점25%화75%,량자차이유통계학의의(P=0.005);p16기인갑기화재악성、단발종류、발병년령조적아조중유증고추세(P＞0.05);(3)갑기화여비갑기화종류조직지간p16 mRNA표체무통계학차이;불동특점적종류중기mRNA표체역무통계학차이,단악성종류p16 mRNA표체여량성종류상비유하강적추세(0.83±0.65대1.12±0.81,P=0.278).결론인PHEO화PGL중,p16기인순합결실화돌변병불상견,단p16기인계동자구갑기화시기실활적주요형식.
Objective To elucidate gene mutation and promoter methylation changes of p16 gene in pheochromocytomas (PHEO) and paragangliomas (PGL) and to assess its relation with tumor clinical characters. Methods A total of 34 tumors (20 PHEO, 14 PG L, 15 benign, 19 malignant) were collected.Direct sequencing of p16 gene after PCR was performed to analyze genetic alterations. Hypermethylation of p16 gene promoter CpG island was analyzed by methylation specific PCR(MSP). In addition, mRNA expression was detected by RT-PCR. Results Homozygous deletion and gene mutation were not observed in 34 PHEO and PGL. Aberrant methylation of p16 gene promoter CpG island was found in 35.3% (12 of 34 tumors, 3 PHEO, 9 PGL). The p16 promoter hypermethylation in PGL was significantly higher than PHEO (P=0. 005). The higher p16 promoter hypermethylation was associated with malignant behavior, tumor number, and younger age at presentation, but no statistical significance, due to the limited number of cases. The p16 mRNA expression in malignant cases was lower than in benign tumors(0.83±0.65 vs 1.12±0.81 ,P=0.278). Conclusion p16 gene homozygous deletion and mutation were not frequent in PHEO and PGL. The promoter hypermethylation is mainly attributed to inactivation of the p16 gene.
