Mutation status of genes encoding RhoA, Rac1, and Cdc42 GTPases in a panel of invasive human colorectal and breast tumors.
OBJECTIVE
The constitutive activation of Ras proteins by point mutation is the most frequently observed oncogene activation in human malignancies. The goal of this study was to investigate whether the constitutive activation of RhoA, Rac1, and Cdc42 proteins by point mutations, which can lead to experimental transformation of cultured cells, actually occurred in a panel of invasive colorectal and breast tumors.


METHODS
We performed denaturing gradient gel electrophoresis and sequencing of transcripts amplified by reverse transcription and PCR for RhoA; we used direct sequencing of PCR-amplified genomic DNA to search for mutations in coding exons of the Rac1 and Cdc42 genes.


RESULTS
Although mutations of the Kras4B and the p53 genes were detected using these methods, no mutation was found in the coding sequences of RhoA, Rac1, and Cdc42 genes, in primary as well as in associated metastasis.


CONCLUSIONS
Point mutations in the coding sequences of genes encoding RhoA, Rac1, and Cdc42 GTPases do not occur at high frequency in invasive breast and colorectal tumors.
Rihet
S
S
Laboratoire de Signalisation Intracellulaire et Oncogènes, INSERM U-528, Institut Curie, Paris, France.
Vielh
P
P
Camonis
J
J
Goud
B
B
Chevillard
S
S
de Gunzburg
J
J
D000230:Adenocarcinoma / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D020764:cdc42 GTP-Binding Protein / Q000235:genetics*; D020830:rac1 GTP-Binding Protein / Q000235:genetics*; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein