Approximately 5% of all GISTs lack functionally relevant mutations inKIT PDGFR, BRAF, or NF1 without deficient SDH complexes (as shown by maintaining expression of SDHB by immunohistochemistry); the oncogenic drivers of “quadruple negative” GIST remain uncertain and possibly more complex than other larger classes of GIST60,63. The gene discussed is NF1; the disease is gastrointestinal stromal tumor.