K-rasRibozyme for Lung Cancer
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Mutations in the K-ras oncogene and mutations or deletions in the tumor suppressor gene p53 are the two most prevalent oncogenetic alterations in human lung cancer. Ras mutations occur primarily in lung adenocarcinomas and small numbers of large cell undifferentiated and squamous cell lung carcinomas, but have not been detected in small cell lung carcinomas. Approximately 30% of lung adenocarcinomas carry a ras mutation. In US and European studies, nearly all mutations occur in the K-ras gene, although N-ras and H-ras mutations have been detected occasionally (1 ). K-ras mutations occur predominantly in codon 12 with a G→T transversion (Table 1 ).
Table 1 K- ras Mutations and Potential Ribozyme Substrate Sites for Adenocarcinoma and Large Cell Carcinoma of the Lung
|
Mutation |
|||
|---|---|---|---|
|
Codon |
Sequence |
Corresponding ribozyme substrate sequence |
% of total mutation |
|
12 |
TGT |
UGU |
55 |
|
12 |
GAT |
GAU |
18 |
|
12 |
GTT |
GUU |
12 |
|
12 |
GCT |
GCU |
3 |
|
12 |
AGT |
AGU |
3 |
|
12 |
TTT |
UUU |
3 |
|
13 |
TGC |
UGC |
6 |
