[Status and clinical analysis of c-kit and PDGFRA mutations in the gastrointestinal stromal tumors].
OBJECTIVE
To investigate the status of c-kit and PDGFRA mutations in the gastrointestinal stromal tumors (GIST) and explore the relationship between the mutations and the clinical features.


METHODS
One hundred and forty-one cases were evaluated for the presence of c-kit and PDGFRA mutations. Exon 9,11,13, 17 of c-kit and exon 12, 18 of PDGFRA were analyzed by PCR amplification and direct sequencing. The relations of clinical features and mutational status were analyzed with statistical tools in this study.


RESULTS
Among the 141 GISTs, c-kit mutations were identified in 76.6% (108/141): 70.2% (99/141) involving exon 11, 5.7% (8/141) involving exon 9, 0.7% (1/141) involving exon 13 and no mutation detected in exon 17. The gene mutations were mostly heterogeneous. The c-kit exon 11 mutational format included deletion (65.7%), point mutation (24.2%) and insert duplications(10.1%).The mutations clustered in the classic "hot spot" at the 5' end of the exon mostly heterogeneous and the second "hot spot" were internal tandem duplications (ITD) at the 3' end of the exon. PDGFRA mutations were totally identified in 12.1%(4/33) of no-c-kit-mutation GISTs and 40%(4/10) of CD117-negative GISTs: all involving exon 18 with the mutations D842V. With the analysis between clinical features and mutation status, the significant difference of gene mutation rate in the different primary tumor organs (chi(2)=7.229, P=0.027, chi(2)=7.000,P=0.03) and no significant differences between the groups of age,gender,tumor size,mitotic rate,grade of malignant potential were found.


CONCLUSIONS
Most GISTs have the c-kit or PDGFRA gene mutation. There are significant difference between mutation and primary tumor organ.
Du
Chun-Yan
CY
Department of Abdominal Surgery, Affiliated Cancer Hospital, Fudan University, Oncology of Shanghai Medical College of Fudan University, Shanghai, China.
Shi
Ying-Qiang
YQ
Zhou
Ye
Y
Fu
Hong
H
Zhao
Guang-Fa
GF
D000328:Adult; D000368:Aged; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*
D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha