AN ETS-RELATED GENE, ERG, IS REARRANGED IN HUMAN MYELOID-LEUKEMIA WITH T(16-21) CHROMOSOMAL TRANSLOCATION

The t(16;21)(p11;q22) translocation is a non-random chromosomal abnorm ality found in several types of myeloid leukemia, which show variable cytomorphological features. We constructed rodent-human somatic cell h ybrids containing the der(16) chromosome from leukemic cells of a pati ent with t(16;21). Using these hybrids, we mapped the translocation br eakpoint on the Not I restriction map of chromosome 21 which we had pr eviously constructed. The result showed the proximity of the breakpoin t to the ERG gene, a member of the ets oncogene superfamily. Polymeras e chain reaction and Southern blot analyses of genomic DNA from the hy brids and from peripheral blood cells and bone marrow cells of patient s with t(16;21) showed that the breakpoints were clustered within a si ngle intron in the coding region of the ERG gene. This finding and the results obtained by Northern blot analysis suggested the formation of a chimeric product(s) by fusion of the ERG gene and an unknown counte rpart gene on chromosome 16.