FLUORESCENCE IN-SITU HYBRIDIZATION CHARACTERIZATION OF NEW TRANSLOCATIONS INVOLVING TEL (ETV6) IN A WIDE SPECTRUM OF HEMATOLOGIC MALIGNANCIES

The ETV6 (also known as TEL) gene on chromosome 12p13 is the target of a number of translocations associated with various hematologic malign ancies. The contribution of ETV6 to leukemogenesis occurs through diff erent mechanisms that involve either its helix-loop-helix dimerization domain or its E26 transformation-specific (ETS) DNA-binding domain. U sing fluorescence in situ hybridization we characterized seven new ETV 6 rearrangements in chronic myeloid leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, and non-Hodgkin's lymphoma. These aberra tions, not always discernible at the cytogenetic level, include a t(5; 12)(q31;p13), t(6;12;17)(p21;p13;q25), t(7;12)(p15;p13), t(7;12)(p12;p 13), t(7;12)(q36;p13), t(12;13)(p13;q12), and a not completely defined t(12;?)(p13;7). Loss or disruption of the second ETV6 allele by a del (12)(p12p13) or by an intragenic ETV6 deletion was detected in two cas es. In six cases the 12p13 breakpoint occurred in the 5' end of ETV6, upstream to exons encoding the HLH domain, whereas the remaining case had a breakpoint between the exons coding for the HLH domain and the e xons coding for the ETS domain of ETV6. These observations provide fur ther evidence for the multiple contributions of ETV6 in the pathogenes is of a wide range of hematologic malignancies. (C) 1998 by The Americ an Society of Hematology.