Rac1 gene mutations in human brain tumours.
OBJECTIVE
Rac1 is a member of the Ras superfamily of small GTPase and plays a fundamental role in cytoskeleton reorganization, regulation of gene expression and cell proliferation, and cellular transformation. Though recent studies point to an involvement of rac1 in tumorigenesis, little is known about the alteration of rac1 gene in human brain tumours.


METHODS
Reverse transcription-polymerase chain reaction (RT-PCR), TA cloning, and DNA sequencing were performed to detect rac1 gene mutations in the surgical specimens of 45 human brain tumours.


RESULTS
Twelve of 45 cases had base changes in the rac1 gene. The frequency of rac1 alterations was seven of 18 meningiomas, three of 14 astrocytomas, one of seven pituitary adenomas, and one of four metastatic brain tumours. No mutation was detected in acoustic neurilemomas. The subtypes of seven meningiomas include three meningotheliomatous, two atypical, one transitional and one angioblastic meningioma. Three astrocytomas had rac1 gene mutation, including one grade II, one grade III, and one grade IV astrocytoma. All of single base changes were transitions, five of them being T to C transitions. Sites of rac1 mutation were found in codons 34, 41 (two cases), 42 (two cases), 43, 44, 46 and 58. These mutations are mainly localized in the putative effector-domain of rac1 gene and may enhance the activity of rac1, which increases the survival of brain tumours.


CONCLUSIONS
Our results suggest that rac1 gene may play a role in some brain tumours of divergent histogenesis and that the alterations of rac1 gene may contribute to tumorigenesis and/or metastasis.
Hwang
S L
SL
Division of Neurosurgery, Kaohsiung Medical University Hospital, 100 Shih Chuan 1st Road, 80708 Kaohsiung, Taiwan, ROC.
Hong
Y R
YR
Sy
W D
WD
Lieu
A S
AS
Lin
C L
CL
Lee
K S
KS
Howng
S L
SL
D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D020830:rac1 GTP-Binding Protein / Q000235:genetics*
D020830:rac1 GTP-Binding Protein