C-kit gene mutation in human gastrointestinal stromal tumors.
OBJECTIVE
To investigate the significance of c-kit gene mutation in gastrointestinal stromal tumors (GIST).


METHODS
Fifty two cases of GIST and 28 cases of other tumors were examined. DNA samples were extracted from paraffin sections and fresh blocks. Exons 11, 9 and 13 of the c-kit gene were amplified by PCR and sequenced.


RESULTS
Mutations of exon 11 were found in 14 of 25 malignant GISTs (56%), mutations of exon 11 of the c-kit gene were revealed in 2 of 19 borderline GISTs (10.5%), and no mutation was found in benign tumors. The mutation rate showed significant difference (chi2=14.39, P<0.01) between malignant and benign GISTs. Most of mutations consisted of the in-frame deletion or replication from 3 to 48 bp in heterozygous and homozygous fashions, None of the mutations disrupted the downstream reading frame of the gene. Point mutations and frame deletions were most frequently observed at codons 550-560, but duplications were most concentrated at codons 570-585. No mutations of exons 9 and 13 were revealed in GISTs, Neither c-kit gene expression nor gene mutations were found in 3 leiomyomas, 8 leiomyosarcomas, 2 schwannomas, 2 malignant peripheral nerve sheath tumors, 2 intra-abdominal fibromatoses, 2 malignant fibrous histiocytomas and 9 adenocarcinomas.


CONCLUSIONS
C-kit gene mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs and can help to differentiate GISTs from other mesenchymal tumors of gastrointestinal tract, such as smooth muscle tumors, schwannomas, etc.
Hou
Ying-Yong
YY
Department of Pathology, Zongshan Hospital, Fudan University, Shanghai 200032, China.
Tan
Yun-Shan
YS
Sun
Meng-Hong
MH
Wei
Yong-Kun
YK
Xu
Jian-Fang
JF
Lu
Shao-Hua
SH
A-Ke-Su
Su-Jie
SJ
Zhou
Yan-Nan
YN
Gao
Feng
F
Zheng
Ai-Hua
AH
Zhang
Tai-Ming
TM
Hou
Wen-Zhong
WZ
Wang
Jian
J
Du
Xiang
X
Zhu
Xiong-Zeng
XZ
D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D017154:Stromal Cells / Q000502:physiology*
D019009:Proto-Oncogene Proteins c-kit