Italiano et al. BMC Cancer 2012, 12:408 http://www.biomedcentral.com/1471-2407/12/408 Page 4 of 7 Figure 1 Sanger sequencing validated a nonsense SDHA exon 2 p.Arg31X mutation in both tumor and normal DNA. The SDHA sequence electropherogram of the tumor DNA contained predominantly the mutated allele (T), indicating relative loss of the wild-type SDHA allele, compared to the normal DNA. Figure 2 ABI sequencing showing a somatic mutation in SDHA exon 2 p. D38V. The normal DNA extracted from this case showed a wild-type sequence for this locus. Discussion The dysregulation of metabolism in cancer has been established for over 80 years. Indeed, one of the first identified biochemical hallmarks of cancer cells was a shift in glucose metabolism from oxidative phosphoryl- ation to aerobic glycolysis [20]. This metabolic conver- sion was considered for a long time a consequence rather than a cause of cancer. However, this vision has been recently challenged by the finding that a significant proportion of familial and apparently sporadic paragan- glioma and pheochromocytoma are related to germline somatic mutation of genes encoding proteins of SDH complex II [21-25]. This complex is a membrane-bound Figure 3 Western blot showing loss of SDHA expression in the young adult GIST carrying a germline SDHA exon 2 mutation p. Arg31X (GIST318, primary gastric tumor; GIST353, liver metastasis), as well as in the young adult GIST carrying a somatic SDHA exon 2 mutation (GIST118, peritoneal metastasis). Remaining WT GIST (GIST#289, 491, 507, 517) lacking SDHA mutations showed preserved SDHA protein expression.