KIT and PDGFRalpha mutational analyses of mixed cell-type gastrointestinal stromal tumours.
OBJECTIVE
To determine whether the epithelioid and spindle components of a mixed cell-type gastrointestinal stromal tumour (GIST) show the same receptor tyrosine kinase mutation and, by inference, the same sensitivity to imatinib.


RESULTS
Six mixed cell-type GISTs were identified from 108 gastric GISTs. Clinicopathological and immunohistochemical data of the six neoplasms were collated. For each neoplasm, DNA was extracted separately from the laser-microdissected epithelioid and spindle components and non-neoplastic tissue and sequenced for KIT and platelet-derived growth factor receptor (PDGFR)alpha mutations. The epithelioid component often showed less CD117 and/or CD34 immunoreactivity than the spindle component of the same mixed cell-type GIST. Four mixed cell-type GISTs showed somatic KIT mutations (deletions in exon 11 in three tumours and an insertion in exon 9 in one tumour) and one showed a somatic PDGFRalpha mutation (point mutation in exon 18); in each of the five cases, both epithelioid and spindle components showed identical mutations.


CONCLUSIONS
The presence of the same receptor tyrosine kinase mutation in both components of a mixed cell-type GIST suggests that both components should be equally responsive to imatinib treatment, and that such mutation is an early key event in the pathogenesis of these neoplasms.
Wong
N A C S
NA
Department of Histopathology, Bristol Royal Infirmary, Bristol, UK. nacs.wong@bristol.ac.uk
Mangwana
S
S
D000368:Aged; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*
D017931:DNA Primers; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha