Oncogene  1990 Mar;5(3):411-6 

RAS mutations in patients following cytotoxic therapy for lymphoma.

Carter G, Hughes DC, Clark RE, McCormick F, Jacobs A, Whittaker JA, Padua RA.

Department of Haematology, University of Wales College of Medicine, Cardiff, UK.

The occurrence of Myelodysplastic Syndrome (MDS) and Acute Myeloblastic
Leukaemia (AML) following cytotoxic therapy for neoplastic disease is well
recognised. RAS mutations are common in patients with MDS and AML. To determine
whether these lesions are found as early markers of secondary disease, we have
studied the incidence of RAS mutations in the peripheral blood of 70 patients in
complete remission from lymphoma. Patients were treated by standard chemotherapy
regimes and/or localised radiotherapy. Treatment had been given 6 months to 14
1/2 years previously and no patient showed any sign of residual disease. Genomic
DNA from peripheral blood leukocytes was amplified in vitro at target codons of
N, K and H RAS genes, and mutations detected by hybridisation with
oligonucleotide probes. RAS mutations were detected in 9 subjects. One patient
with an N12 valine (Val) substitution had been in complete remission from
Hodgkin's disease (HD) for 9 years. DNA from this patient registered in a nude
mouse tumorigenicity assay (NMT). The N12 Val mutation was not detected in the
original tumour tissue from the same patient. A second patient in remission from
HD showed evidence of co-existent N12 cysteine (Cys) and N13 valine (Val)
substitutions which were not detected in presentation material or unaffected
tissues. All patients are currently haematologically normal, indicating that
clones of mutant RAS bearing cells may be detected prior to any overt sign of
disease.

PMID: 2179819 [PubMed - indexed for MEDLINE]