Polymorphism of the proto-oncogene ETS-1 in hematological malignancies.

We studied a novel restriction fragment length polymorphism (RFLP) of the proto-oncogenes ETS-1 that we detected in a patient with an acute monocytic leukemia by the presence of two, 3.7 and 10 kb, Xbal fragments on Southern blots of DNA from blast cells and remission blood samples. RFLP analysis of a series of 114 normal donors revealed that only four (3.6%) shared the 10 kb fragment. By contrast, this unusual allele was found in 20 (all lymphocytic or monocytic) of 108 (18.5%) hematological malignancies (p less than 0.001). DNA sequence analysis indicated the disappearance in the rare allele of a Xbal site due to a single point mutation at the 3' end of ETS-1 locus. Molecular consequences of this mutation point to a possible pathogenic involvement of ETS-1 in these disorders and to the question of genetic susceptibility to hematological malignancies.