Deletion of the KIT gene is associated with liver metastasis and poor prognosis in patients with gastrointestinal stromal tumor in the stomach.

Abstract

The goal of this study was to investigate the association of mutations in the KIT gene and the platelet-derived growth factor receptor alpha (PDGFRA) gene with clinicopathological features of patients with gastrointestinal stromal tumor (GIST) localized in the stomach. We evaluated 56 gastric GISTs for KIT and PDGFRA mutations. DNA was extracted from paraffin-embedded tumor specimens, and exons 9, 11, 13 and 17 of the KIT gene and exons 12 and 18 of the PDGFRA gene were amplified by polymerase chain reaction and sequenced. The genetic features were then compared with the clinicopathological features. Immunohistochemistry was performed for KIT, CD34, Ki-67 (as a marker of cell proliferation) and CD31 (as a marker of microvessel density), and apoptosis was assessed by in situ DNA nick-end labeling. Thirty-four (61%) of the 56 GISTs had a mutation in exon 11 of KIT, and 2 (4%) had a mutation in exon 13 of KIT. Deletions in exon 11 of KIT were the most common mutation encountered in the present study. No mutations were found in exon 9 or 17 of KIT. Six of the 20 GISTs lacking KIT mutations had a mutation in exon 18 of PDGFRA, and 1 had a mutation in exon 12 of PDGFRA. The KIT mutation-positive GISTs showed more frequent liver metastases and higher mortality than KIT mutation-negative GISTs. Our data indicate that KIT mutations, especially deletions in exon 11, are markers of poor prognosis for gastric GISTs.

• Authors: Songde Cho, Yasuhiko Kitadai, Shigeto Yoshida, Shinji Tanaka, Masaharu Yoshihara, Kazuhiro Yoshida, Kazuaki Chayama
• Journal: International journal of oncology (Int J Oncol) Vol. 28 Issue 6 Pg. 1361-7 (Jun 2006) ISSN: 1019-6439 [Print] Greece
• PMID: 16685437 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Antigens, CD34
• Biomarkers, Tumor
• DNA, Neoplasm
• Ki-67 Antigen
• Platelet Endothelial Cell Adhesion Molecule-1
• Proto-Oncogene Proteins c-kit
• Receptor, Platelet-Derived Growth Factor alpha

Topics

• Antigens, CD (analysis)
• Antigens, CD34 (analysis)
• Base Sequence
• Biomarkers, Tumor (analysis)
• DNA, Neoplasm (genetics, isolation & purification)
• Exons
• Gastrointestinal Neoplasms (genetics, mortality, pathology)
• Humans
• Immunohistochemistry
• Ki-67 Antigen (analysis)
• Liver Neoplasms (genetics, mortality, secondary)
• Mutation
• Platelet Endothelial Cell Adhesion Molecule-1 (analysis)
• Polymerase Chain Reaction
• Proto-Oncogene Proteins c-kit (genetics)
• Receptor, Platelet-Derived Growth Factor alpha (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Sequence Deletion
• Stomach Neoplasms (genetics, mortality, pathology)
• Survival Analysis