FUSION OF THE FUS GENE WITH ERG IN ACUTE MYELOID-LEUKEMIA WITH T(16-21)(P11-Q22)

It has been shown that the gene ERG in 21q22 is rearranged in the t(16 ;21)(p11;q22) associated with acute myeloid leukemia (AML). ERG is a m ember of the ETS gene family and is fused with EWS in a subset of Ewin g's sarcomas. EWS in 22q12 has a very high homology with FUS (also cal led TLS) in 16p11; the latter gene is rearranged in the t(12;16)(q13;p 11) that characterizes myxoid liposarcoma To investigate whether FUS i s involved in the t(16;21) of AML, we used the Southern blot technique and polymerase chain reaction (PCR) to examine the bone marrow of a 3 -year-old boy with a t(16;21)(p11;q22)-positive AML. Hybridization of Southern blot filters containing digested DNA with probes for FUS and ERG showed both germline and aberrant fragments, Using specific primer s for the 5' part of FUS and the 3' part of ERG, we amplified a 4.4 kb genomic FUS/ERG DNA fragment from the leukemic sample. In a second PC R experiment, in which we used primers upstream of the 5' part of ERG and downstream of the 3' part of FUS, a 5.6 kb fragment was amplified. Blotting and hybridization with specific probes for FUS and ERG revea led that the amplified fragments consisted of FUS/ERG and ERG/FUS hybr id DNA. Both PCR fragments, when used as probes, detected germline ERG and FUS as well as aberrant fragments on Southern blot filters. The r esults suggest that the t(16;21) in AML leads to rearrangement and fus ion of the FUS and ERG genes. This is the first example in which two g enes, each known to recombine with other genes in different solid rumo r types (FUS in myxoid liposarcoma and ERG in Ewing's sarcoma), are fu sed in a hematologic malignancy. (C) 1994 Wiley-Liss, Inc.