Point mutations of the topoisomerase IIalpha gene in patients with small cell lung cancer treated with etoposide.
Reverse transcription-PCR-single-strand conformation polymorphism analysis was performed to detect topoisomerase IIalpha mutations using total RNA from 19 bronchial biopsy specimens obtained from 13 patients with small cell lung cancer. An abnormally migrating single-strand conformation polymorphism band was observed in one tumor sample from a patient treated with etoposide-containing chemotherapy. DNA sequence analysis of this tumor showed two transversions at codons 486 (G to A) and 494 (A to G), resulting in two missense mutations (Arg to Lys and Glu to Gly, respectively). The codon 486 mutation was identical to that previously found in two cell lines selected for amsacrine resistance. These results demonstrate that mutations of topoisomerase IIalpha occur in patients with small cell lung cancer. The significance of these mutations in the development of resistance to etoposide needs further investigation.
Kubo
A
A
Department of Internal Medicine, Osaka Prefectural Habikino Hospital, Japan.
Yoshikawa
A
A
Hirashima
T
T
Masuda
N
N
Takada
M
M
Takahara
J
J
Fukuoka
M
M
Nakagawa
K
K
D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000235:genetics*; D003062:Codon / Q000187:drug effects / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D000972:Antineoplastic Agents, Phytogenic; D003062:Codon; D005047:Etoposide; D004317:Doxorubicin; D004250:DNA Topoisomerases, Type II