The loss of SDH activity has important consequences for the pathogenesis of these tumors.108, 109Approximately a half of SDH-deficient GISTs are related to hypermethylation of the SDHC promoter, which cause decrease of SDHC proteins, germline mutations in SDHA occur in around 30%, whereas those in SDHB, SDHC, and SDHD are less frequent.110SDH-deficient GISTs exhibit specific clinical features and pathological characteristics, are commonly multifocal, and often associated with metastatic disease. The gene discussed is SDHB; the disease is metastatic neoplasm.