| Abstract: | This study aimed to investigate the association of SDH gene mutations and promoter methylation with succinate dehydrogenase‐deficient gastrointestinal stromal tumors (SDH‐deficient GISTs) and to further discuss the potential molecular mechanisms underlying SDHB expression loss in these tumors. First, a total of 26 patients with SDH‐deficient GISTs were selected by identifying the loss of SDHB protein expression and wild‐type for KIT and PDGFRa mutations. Then SDH gene mutations and promoter methylation were detected by DNA sequencing and methylation‐specific polymerase chain reaction, respectively, and the clinical and pathological data of SDH‐deficient GISTs patients were collected and analyzed accordingly. The results of genetic testing demonstrated that 38.46% (10/26) of these patients harbored mutations in SDHB, SDHC, and SDHD genes (3 cases with double mutations). Besides, aberrant promoter methylation of SDH genes was detected in 10 out of 26 cases (38.46%), including 8 cases in SDHA gene, 3 cases in SDHB gene, 1 case in both SDHA and SDHB genes. It is suggested that SDH gene mutations and promoter methylation may contribute to the loss of SDH protein expression in sporadic SDH‐deficient GISTs. This study indicated that the genetic and epigenetic alterations of SDH genes may occur during tumor formation. |
