A patient with a newly diagnosed gastrointestinal stromal tumor (GIST) undergoes molecular testing. Approximately 85% of GISTs harbor an activating mutation in which proto-oncogene, making imatinib mesylate the first-line targeted therapy?
- A PDGFRA
- B RET
- C KIT (CD117) ✓
- D ALK
Correct answer: C. KIT (CD117)
Explanation
GISTs predominantly harbor activating mutations in KIT (c-KIT, CD117), a receptor tyrosine kinase normally expressed in the interstitial cells of Cajal. ~85% have KIT mutations; ~10% have PDGFRA mutations (which may be imatinib-resistant depending on exon); ~5% are wild-type. Imatinib inhibits KIT and PDGFRA, producing dramatic responses in KIT-mutant GISTs. Immunohistochemically, GISTs are CD117+, DOG1+ and CD34+.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.