CAJ | 학술논문

目的检测家族性嗜铬细胞瘤/副神经节瘤(PHEO/PGL)中编码琥珀酸脱氢酶(succinate dehydrogenase,SDH)复合体亚单位的核基因以及RET、VHL基因突变和SDHB的DNA甲基化程度,探讨家族性PHEO/PGL基因突变和DNA甲基化与其发病机制的关系.方法对2008年10月至2011年4月97例PHEO/PGL患者进行了SDHB、SDHC、SDHD、SDHAF2、VHL和RET等胚系突变基因的分析.对SDHB基因(1q36.1～1q35,外显子1～8),SDHC基因(1q21,外显子1～5),SDHD基因(11q23,外显子1～4),SDHAF2基因(11q12.2,外显子1～4),RET原癌基因(10q11.2,外显子10、11、13、14及15、16)和VHL基因 (3p25.3,外显子1～3)等进行DNA序列分析.同时检测PHEO/PGL患者外周血样本SDHB启动子区的甲基化程度,与临床特点包括年龄、肿瘤直径、多发病变和内分泌检查等结果行相关分析.结果 97例患者中基因突变17例(17.5％),其中SDHB基因突变7例(7.2％),均位于腹膜后,恶变者4例;RET原癌基因突变8例(8.2％);VHL基因突变2例(2.1％).检测到7例PHEO/ PGL的外周血样本SDHB启动子区的DNA甲基化,有或无甲基化两组的良/恶性、单/多发和肿瘤直径比较差异有统计学意义(P＜0.01).结论 SDHB突变多见于腹膜后的PGL和恶变的PGL; SDHB基因DNA甲基化程度较高,可能是其恶变的机制之一.推荐对PHEO/PGL患者进行基因筛查.
목적 검측가족성기락세포류/부신경절류(PHEO/PGL)중편마호박산탈경매(succinate dehydrogenase,SDH)복합체아단위적핵기인이급RET、VHL기인돌변화SDHB적DNA갑기화정도,탐토가족성PHEO/PGL기인돌변화DNA갑기화여기발병궤제적관계.방법 대2008년10월지2011년4월97례PHEO/PGL환자진행료SDHB、SDHC、SDHD、SDHAF2、VHL화RET등배계돌변기인적분석.대SDHB기인(1q36.1～1q35,외현자1～8),SDHC기인(1q21,외현자1～5),SDHD기인(11q23,외현자1～4),SDHAF2기인(11q12.2,외현자1～4),RET원암기인(10q11.2,외현자10、11、13、14급15、16)화VHL기인 (3p25.3,외현자1～3)등진행DNA서렬분석.동시검측PHEO/PGL환자외주혈양본SDHB계동자구적갑기화정도,여림상특점포괄년령、종류직경、다발병변화내분비검사등결과행상관분석.결과 97례환자중기인돌변17례(17.5％),기중SDHB기인돌변7례(7.2％),균위우복막후,악변자4례;RET원암기인돌변8례(8.2％);VHL기인돌변2례(2.1％).검측도7례PHEO/ PGL적외주혈양본SDHB계동자구적DNA갑기화,유혹무갑기화량조적량/악성、단/다발화종류직경비교차이유통계학의의(P＜0.01).결론 SDHB돌변다견우복막후적PGL화악변적PGL; SDHB기인DNA갑기화정도교고,가능시기악변적궤제지일.추천대PHEO/PGL환자진행기인사사.
Objective To detect the genetic mutations of succinate dehydrogenase B (SDHB),SDHC,SDHD,SDHAF2 and RET,VHL in hereditary pheochromocytoma (PHEO) paraganglioma (PGL) syndrome in order to analyze the relationship between the pathogenesis and SDHx mutations and DNA methylation.Methods SDH genes,VHL and RET were analyzed for germline mutations in 97 PHEOs/PGLs patients.Correlations were analyzed between the results and the clinical characteristics including age,tumor localization,multifocality,24 h urine CA,IGF and NSE.Direct DNA sequence analysis was carried out for SDHB (1q36.1-1q35,exons1-8),SDHC (1q21,exons 1-5),SDHD (11q23,exons 1-4),SDHAF2 (11q12.2,exons 1-4),RET (10q11.2,exons10,11,13,14&15,and 16) and VHL (3p25.3,exons 1-3) genes,and promoter region methylation of SDHB was detected in PHEO/PGL peripheral blood samples.Results Germinal mutations were found in 17 patients (17.5％),with 8 cases in RET proto-oncogene (8.2％),7 cases in SDHB genes (7.2％) and 2 cases in VHL gene (2.1％).The comparison of some of the clinical features in two groups (with and without promoter region methylation of SDHB) showed significant differences (P＜0.01).Conclusions Genetic predisposition is frequent in chromaffin tissue tumors,indicating that DNA analysis is necessary.The mutation of SDHB is highly associated with abdominal PGL and the following distant metastasis (malignant PGL).