Longitudinal analysis of point mutations of the N-ras proto-oncogene in
patients with myelodysplasia using archived blood smears
H van Kamp, C de Pijper, M Verlaan-de Vries, JL Bos, CH Leeksma, H Kerkhofs, R Willemze, WE Fibbe and JE Landegent
Department of Hematology, University Medical Center, Leiden, The
Netherlands.
We performed a longitudinal analysis of point mutations of the N-ras
proto-oncogene in patients with myelodysplasia and a follow-up of at least
2.5 years after diagnosis. Point mutations at codons 12, 13, and 61 of the
N-ras oncogene were analyzed after in vitro amplification of N-ras specific
sequences followed by dot-blot hybridization. Lysed cells scraped from
archived blood and bone marrow smears were used as template for a
polymerase chain reaction. In 3 of 90 patients tested (3.3%), a mutation in
codon 12 could be detected in the most recent blood smears. All available
blood and bone marrow samples of these patients were subsequently analyzed
for the occurrence of that particular mutation. In all three cases the
mutation was not detectable at diagnosis, but was acquired later during the
course of the disease. In two of these patients this event was associated
with rapid deterioration and transformation to acute leukemia. However, the
third patient showed a protracted course during a period of 5 years after
acquisition of the mutation. These results indicate that activation of the
N-ras protooncogene in these three patients represents a secondary
phenomenon associated with disease progression in some cases, but
compatible with stable disease in others.
Volume 79,
Issue 5,
pp. 1266-1270,
03/01/1992
Copyright © 1992 by The American Society of Hematology
