Rapid communicationGain-of-function mutations of platelet-derived growth factor receptor α gene in gastrointestinal stromal tumors☆
Section snippets
Patients and tissue specimens
We collected 70 fresh samples of GIST tissues during surgical procedures at Osaka University Medical School and its affiliated hospitals. Paraffin sections (3 μm thick) of the formalin-fixed tissues were cut and used for H&E staining and immunohistochemistry. Mesenchymal tumors were identified to be GISTs when they were positive for KIT and/or CD34 by immunohistochemistry.1, 2 Genomic DNA was extracted from paraffin sections (10 μm thick), and used for the sequencing of exon 9 of PDGFR α DNA.
Identification of KIT mutations in GISTs and expression of PDGFR α in GISTs
The whole coding region of KIT cDNA was sequenced in 70 GISTs. Deletion, insertion, and/or point mutation were found at the juxtamembrane domain in 58 GISTs, and duplication of 2 amino acids (codons 501-Ala and 502-Tyr) were found at the extracellular domain in 4 GISTs. No KIT mutations were found in the remaining 8 GISTs.
By Northern blotting, PDGFR α transcripts were detected in most GISTs, and there was a tendency for the expression levels to be stronger in GISTs without KIT mutations than in
Discussion
We found gain-of-function mutations of PDGFR α gene in 5 of 8 GISTs without KIT mutations. No such PDGFR α mutations were found in GISTs with KIT mutations. All GISTs with the gain-of-function mutations of PDGFR α gene primarily developed in the stomach. One GIST patient with 561-Val to Asp PDGFR α mutation died of cancerous peritoneal dissemination 6 years after the primary surgery. The other GIST patient with 561-Val to Asp PDGFR α mutation had local recurrence, but the lesion appeared to be
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Supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan.