Point mutations in both transforming and non-transforming codons of the N-ras proto-oncogene of Ph+ leukemias

G. Rovera, B. A. Reichard, S. Hudson, S. Bittenbender, Masao Yamada, O. Tournay, H. D. Preisler

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The distribution and frequency of point mutations in the first and second coding exons of the N-ras proto-oncogene was examined in 6 cases of Philadelphia positive (Ph+) hemopoietic malignancies. To increase the detection sensitivity of the mutations and to estimate more accurately the frequency of abnormal alleles in the hemopoietic cell population, a polymerase chain reaction (PCR)/shotgun cloning/double stranded DNA sequencing method was used. Mutations activating the ras oncogenes involving codon 61 were observed in 5 out of 6 cases; in one of these cases (CML3), mutation at codon 61 involved a two base transition. Mutations involving codon 59 were also observed in one case (CML1). In longitudinal studies of 3 cases of chronic myelogenous leukemia samples obtained at the time of initial diagnosis and 5 to 7 years later, a multiplicity of mutations were detected at the time of initial diagnosis prior to any therapy. In one case (CML3), a mutation in codon 61 detected at diagnosis was still present 5 years later, in a second case (CML1) a mutation in codon 61 appeared during the course of the disease and persisted for at least one year, and in the third case (CML2) a mutation in codon 61 was present at diagnosis but absent 5 years later. In one instance (CML1) a mutation in codon 59 was present at the time of initial diagnosis but was not detectable in later samples. Several other point mutations leading to aminoacid changes were scattered predominately through the second exon but were not consistently detected in longitudinal studies on cells from the same patient. The data suggest that there is considerable genetic instability in the 2nd exon of N-ras in the myeloid leukemias but in every case a small subset of cells contains the mutations and these cells do not have a proliferative advantage.

Original languageEnglish
Pages (from-to)867-872
Number of pages6
JournalOncogene
Volume4
Issue number7
Publication statusPublished - 1989
Externally publishedYes

Fingerprint

ras Genes
Proto-Oncogenes
Point Mutation
Codon
Leukemia
Mutation
Exons
Longitudinal Studies
Myeloid Leukemia
Firearms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
DNA Sequence Analysis
Gene Frequency
Organism Cloning
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Rovera, G., Reichard, B. A., Hudson, S., Bittenbender, S., Yamada, M., Tournay, O., & Preisler, H. D. (1989). Point mutations in both transforming and non-transforming codons of the N-ras proto-oncogene of Ph+ leukemias. Oncogene, 4(7), 867-872.

Point mutations in both transforming and non-transforming codons of the N-ras proto-oncogene of Ph+ leukemias. / Rovera, G.; Reichard, B. A.; Hudson, S.; Bittenbender, S.; Yamada, Masao; Tournay, O.; Preisler, H. D.

In: Oncogene, Vol. 4, No. 7, 1989, p. 867-872.

Research output: Contribution to journalArticle

Rovera, G, Reichard, BA, Hudson, S, Bittenbender, S, Yamada, M, Tournay, O & Preisler, HD 1989, 'Point mutations in both transforming and non-transforming codons of the N-ras proto-oncogene of Ph+ leukemias', Oncogene, vol. 4, no. 7, pp. 867-872.
Rovera G, Reichard BA, Hudson S, Bittenbender S, Yamada M, Tournay O et al. Point mutations in both transforming and non-transforming codons of the N-ras proto-oncogene of Ph+ leukemias. Oncogene. 1989;4(7):867-872.
Rovera, G. ; Reichard, B. A. ; Hudson, S. ; Bittenbender, S. ; Yamada, Masao ; Tournay, O. ; Preisler, H. D. / Point mutations in both transforming and non-transforming codons of the N-ras proto-oncogene of Ph+ leukemias. In: Oncogene. 1989 ; Vol. 4, No. 7. pp. 867-872.
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