Gastrointestinal stromal tumors carrying PDGFRα mutations occur preferentially in the stomach and exhibit an epithelioid or mixed phenotype

Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?

“…However, PDGFRα expression and activating mutations have been reported in gastrointestinal stromal tumors (GIST) [28] . Most interestingly, PDGFRα mutated GIST displayed an epitheloid or mixed phenotype and were exclusively located in the stomach, whereas PDGFRα wildtype tumors also occurred in the small bowel [29] . PDGFRb expression in gastric adenocarcinoma was only described once in 1992 by Chung and colleagues analyzing three tumor samples [30] .…”

Genetic aberrations of gastrointestinal stromal tumors

“…They found PDGFRA -mutated tumors were preferentially located in the stomach, whereas GIST with exon 9 and 13 KIT mutations occurred predominantly in the small bowel. Furthermore, GIST carrying PDGFRA mutations displayed an epithelioid or mixed phenotype, while KIT -mutated GIST almost always exhibited a spindled or mixed histologic pattern 32. The investigators also found that some mutations were located in the second kinase domain of PDGFRA , including 16 point mutations and 4 larger deletions of 9 to 12 bp.…”

Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network

“…A classic example of this is mutational profiling of KIT, PDGFRA, and other genes to predict sensitivity of gastrointestinal stromal tumors (GISTs) to imatinib and other KIT/PDGFRA tyrosine kinase inhibitors. [6][7][8][9][10][11] More recently, the discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as pan-tumor oncogenic drivers has provided new precision medicinebased treatment options for a subset of patients with sarcoma. 12 The rarity and diagnostic complexity of this particular biomarker raise a number of questions and challenges for clinicians.…”