Mutation analysis of the N-ras proto-oncogene in active and remission phase of human acute leukemias.
DNA isolated from blood or bone-marrow samples from 18 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) was analyzed for the presence of mutations in the N-ras gene. Using synthetic oligonucleotide probes we detected mutations in 5 cases of ANLL; 4 GGT----GAT transitions in codon 12 and one CAA----AAA transversion in codon 61. One case exhibited homozygosity for the mutation. No mutations could be detected at these codons in the DNA of the 14 ALL patients. In a follow-up study with 3 of the above 5 patients, the mutation could no longer be detected in 2 cases following successful induction of clinical remission by chemotherapy. However, the mutated N-ras persisted in one patient who did not achieve remission. We show that oligonucleotide hybridization is a sensitive assay for the detection of N-ras point mutations, which in ANLL could be used to follow the fate of the leukemic clone during (and after) therapy.
Senn
H P
HP
Friedrich-Miescher Institut, Basel, Switzerland.
Trân-Thang
C
C
Wodnar-Filipowicz
A
A
Jiricny
J
J
Fopp
M
M
Gratwohl
A
A
Signer
E
E
Weber
W
W
Moroni
C
C
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D003062:Codon; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D011905:Genes, ras; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000235:genetics*; D007945:Leukemia, Lymphoid / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009693:Nucleic Acid Hybridization; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes
D003062:Codon; D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas