Amplification of RNA and DNA specific for erb B in unbalanced 1;7 chromosomal translocation associated with myelodysplastic syndrome.
Previous work has established the presence of an unbalanced chromosome abnormality [+der(1),t(1;7)(p11;p11)] in some therapy-associated myelodysplastic disorders. Recently the EGF receptor has been found to reside at 7p11. Using a probe specific for erb B oncogene, which encodes a truncated form of the EGF receptor, we examined RNA and DNA derived from bone marrow and peripheral blood mononuclear cells from three patients with myelodysplastic syndromes (MDS) and one with acute lymphocytic leukemia (ALL), all bearing an abnormal clone in their bone marrow with a similar unbalanced 1;7 translocation. DNA-excess slot blot hybridization to 5'-32p-labeled cellular RNA revealed from ten- to thirtyfold enhancement in accumulation of mRNA specific for erb B in both peripheral blood and bone marrow cells of the three MDS patients when compared to normal controls. In addition, enhancement of H-ras mRNA accumulation was detected in some, though expression of other genes such as actin, N-ras, myc, src, B-lym, and 20 other genes was not found to be enhanced. Increased erb B expression was not apparent in mononuclear cells from patients with other hematologic disorders such as chronic lymphocytic leukemia, Hodgkin's disease, or lymphoma. Southern blot analysis of restriction-enzyme-cleaved DNA from three MDS patients with an unbalanced 1;7 translocation revealed that erb B gene was amplified at least twentyfold in peripheral blood white blood cells, while levels of actin hybridization were comparable to those of the controls. No such amplification was evident in the ALL patient. Our data suggest that +der(1),t(1;7)(p11;p11) chromosomal anomalies can be specifically associated with amplification of erb B DNA and RNA sequences.
Woloschak
G E
GE
Dewald
G W
GW
Bahn
R S
RS
Kyle
R A
RA
Greipp
P R
PR
Ash
R C
RC
D002878:Chromosomes, Human, Pair 1; D002897:Chromosomes, Human, Pair 7; D004247:DNA / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D007945:Leukemia, Lymphoid / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics*; D014178:Translocation, Genetic
D012333:RNA, Messenger; D004247:DNA; D066246:ErbB Receptors