[Analysis of c-kit gene mutations in gastrointestinal stromal tumors].
OBJECTIVE
To define the frequency and spectrum of c-kit gene mutations in gastrointestinal stromal tumors (GIST).


METHODS
Fifty two cases of GIST and 28 cases of other tumors were examined for mutations in exon 11, 9 and 13 of c-kit gene using PCR amplification and DNA sequencing.


RESULTS
Fourteen out of 25 malignant GIST (56%), while 2 of 27 benign and borderline GIST (7.4%) revealed mutations in exon 11 of c-kit gene (P < 0.01). Most of the mutations consisted of in-frame deletion or replication from 3 to 48 bp in heterozygous and homozygous fashions, but none of the mutations disrupted the downstream reading frame of the gene. Point mutation and deletion concentrated at 550 - 570 codons but replication clustered within 570 - 585 codons. The mutation pattern in recurrence tissues was the same as the primary ones. Normal tissues adjacent to GIST with or without c-kit gene mutations showed wild type c-kit gene sequence. No mutation was found in exon 9 and 13. Neither c-kit gene expression nor gene mutations was found in 3 leiomyomas, 8 leiomyosarcomas, 2 schwannomas, 2 intra-abdomenal fibromitoses and 8 adenocarcinomas.


CONCLUSIONS
The mutations in exon 11 of c-kit gene might partially represent one of the molecular mechanisms of GIST. It can be used as a marker for distinguishing benignancy and malignancy of GIST. The mutations did not involve the reading frame. Except for long frame deletion, most mutations also did not affect protein expression. Mutation of c-kit gene in GIST provides a new genotypic marker to distinguish GIST from authentic leiomyomas, leiomyosarcomas, schwannomas and etc.
Hou
Ying-yong
YY
Department of Pathology, Zhongshan Hospital, Medical College of Fudan University, Shanghai 200032, China.
Sun
Meng-hong
MH
Tan
Yun-shan
YS
Wei
Yong-kun
YK
Lu
Xiao-yu
XY
Zhang
Tai-ming
TM
Du
Xiang
X
Wang
Jian
J
Zhu
Xiong-zeng
XZ
D001483:Base Sequence; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics*; D011519:Proto-Oncogenes
D019009:Proto-Oncogene Proteins c-kit