家族性副神经节瘤中SDHD SDHB基因突变分析  

Analysis of SDHD and SDHB Gene Mutations in Paraganglioma Patients

作　　者：李亦工[1] 郑向前[1] 冯影[1] 魏松锋[1] 于洋[1] 李小龙[1] 高明[1] 

机构地区：[1]天津市肿瘤防治重点实验室天津医科大学附属肿瘤医院甲状腺颈部肿瘤科,天津市300060

出　　处：《中国肿瘤临床》2010年第16期911-913,920,共4页Chinese Journal of Clinical Oncology

摘　　要：目的:探讨SDHD、SDHB基因突变在我国副神经节瘤(PGL)患者中的发生状况,为PGL分子诊断和分子遗传学的深入研究提供基础。方法:收集天津医科大学附属肿瘤医院2006年4月～2007年12月间收治的具有完整临床及病理资料的8例散发性副神经节瘤患者、1例家族性副神经节瘤患者及其4位亲属的外周血标本。留取18例正常人外周血标本作为对照。扩增SDHD、SDHB基因各外显子,纯化后直接进行DNA序列测定,将测序结果与美国生物技术信息中心公布的标准序列比对。结果:家族性PGL病例检测到SDHD基因杂合性错义突变,8例散发性副神经节瘤病例未检测到SDHD基因外显子突变。2例散发性PGL病例携带SDHB基因第一外显子同义突变,发病时间早于不伴该同义突变者,且病理上均为恶性。家族性病例未检测到SDHB基因突变。结论:家族性PGL病例携带SDHD基因突变,而散发性PGL病例中未发现SDHD基因突变,提示SDHD基因突变可能是国人家族性副神经节瘤发病的分子基础之一。散发性副神经节瘤病例检测到SDHB基因第一外显子同义突变A6A,有该突变的患者病理上均为恶性,提示A6A可能影响副神经节瘤的表型。Objective： To investigate the prevalence of SDHD and SDHB mutations in patients with paraganglioma （PGL） and to provide the basis for further study of molecular diagnosis and molecular genetics of PGL. Methods： Eight sporadic PGL cases and one familial PGL case with complete clinical and pathological data were collected. All of them were preliminarily diagnosed in our hospital duing April 2006 and December 2007. We also collected blood samples from 18 nor- mal people and 4 family members of the familial cases. Amplified fragments of SDHD and SDHB exons obtained through PCR were sequenced directly after purification. We used the software of BLAST to compare the results of sequencing with the standard sequences published in the NCBI net. Results： The familial case carried a heterozygotic missense mutation in SDHD. None of the 8 sporadic cases had mutations in SDHD. Two of the 8 sporadic cases carried samesense germline mutations in SDHB-exon 1 and both of them had malignant leisions and an early onset. SDHB gene mutation was not found in the familial case. Conclusion： The mutation in SDHD gene may be a molecular mechnism of paraganglioma genesis. Genetic testing of familial cases is useful for identification of mutation carriers and early detection. Samesense mutation in SDHB-exon 1 A6A may affect the phenotype of paraganglioma.

关 键 词：副神经节瘤 琥珀酸脱氢酶 基因突变 颈动脉体瘤 

分 类 号：R730.4[医药卫生—肿瘤]