Fluorescence In Situ Hybridization Characterization of New
Translocations Involving TEL (ETV6) in a Wide Spectrum of
Hematologic Malignancies
Iwona Wlodarska,
Roberta La Starza,
Mathijs Baens,
Judith Dierlamm,
Ann Uyttebroeck,
Dominik Selleslag,
Adrien Francine,
Cristina Mecucci,
Anne Hagemeijer,
Herman Van den Berghe, and
Peter Marynen
From the Center for Human Genetics and Flanders Interuniversity
Institute of Biotechnology, and the Department of Pediatrics,
University of Leuven, Leuven, Belgium; the Hematology and Bone Marrow
Transplantation Unit, University of Perugia, Perugia, Italy; the
Department of Hematology, AZ St Jan, Brugge, Belgium; and the
Department of Hemato-Oncology, CHR Citadelle, Liege, Belgium.
The ETV6 (also known as TEL) gene on chromosome
12p13 is the target of a number of translocations associated with
various hematologic malignancies. The contribution of ETV6 to
leukemogenesis occurs through different mechanisms that involve either
its helix-loop-helix dimerization domain or its E26
transformation-specific (ETS) DNA-binding domain. Using
fluorescence in situ hybridization we characterized seven new
ETV6 rearrangements in chronic myeloid leukemia, acute myeloid
leukemia, acute lymphoblastic leukemia, and non-Hodgkin's lymphoma.
These aberrations, 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;p13), t(7;12)(q36;p13), t(12;13)(p13;q12), and a not completely defined t(12;?)(p13;?). Loss or disruption of the second ETV6 allele by a del(12)(p12p13) or by an intragenic
ETV6 deletion was detected in two cases. 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 exons
coding for the ETS domain of ETV6. These observations provide
further evidence for the multiple contributions of ETV6 in the
pathogenesis of a wide range of hematologic malignancies.
Blood, Vol. 91 No. 4 (February 15), 1998:
pp. 1399-1406
© 1998 by The American Society of Hematology.
