散发性SDH缺陷型胃肠道间质瘤26例临床及分子病理学特征

目的观察散发性琥珀酸脱氢酶(succinate dehydrogenase,SDH)缺陷型胃肠道间质瘤(gastrointestinal stromal tumor,GIST)的临床病理特点、免疫表型、分子遗传学改变,并探讨潜在的分子机制。方法采用甲基化特异性PCR、直接测序法检测26例散发性SDH缺陷型GIST,并分析其临床病理学、免疫表型及分子遗传学特点。结果26例GIST中15例(57.69%)存在至少一项SDH基因异常,38.46%(10/26)检测到SDHB、SDHC、SDHD基因突变,其中3例双突变。甲基化特异性PCR技术检测出38.46%(10/26)病例发生基因启动子甲基化:SDHA基因8例,SDHB基因3例,其中1例同时甲基化。结论通过分析SDH缺陷型GIST的形态学特征、免疫表型和分子生物学特征,提示SDH基因突变及甲基化均是肿瘤抑制因子失活的重要机制,在肿瘤发生、发展中发挥重要作用。SDH突变与SDH启动子甲基化同时发生,提示存在基因多种异常共同作用的可能性。

Clinical and molecular pathological features of gastrointestinal stromal tumors with sporadic SDH-deficiency:a report of 26 cases

Purpose This study aimed to investigate the clinical,pathological,genetic change of succinate dehydrogenase(SDH)gene in SDH-deficient gastrointestinal stromal tumors(GIST),and to further discuss its potential molecular mechanisms.Methods Methylation-specific polymerase chain reaction(PCR)and DNA sequencing were used to detected 26 cases of sporadic SDH deficiency GIST,and to analyze the clinicopathological,immunophenotypic and molecular genetic characteristics.Results Among the 26 cases of GIST,15 cases(57.69%)had at least one abnormality of SDH gene,and 38.46%(10/26)of these cases harbored mutations in SDHB,SDHC and SDHD genes,of which 3 cases had double mutations.Methylation-specific PCR technique detected in 38.46%(10/26)cases with aberrant promoter methylation of genes,including eight cases with SDHA gene,three with SDHB gene,and one case with both.Conclusion It is suggested that SDH gene mutation and methylation are important mechanisms of tumor suppressor inactivation and play a potential role during tumor formation by analyzing the clinical,pathological,molecular features of sporadic SDH-deficient GIST.The simultaneous occurrence of SDH promoter methylation suggests that there is the possibility of multiple abnormalities in the gene.