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Blood, Vol. 94 No. 6 (September 15), 1999:
pp. 2072-2079
The (4;11)(q21;p15) Translocation Fuses the NUP98 and
RAP1GDS1 Genes and Is Recurrent in T-Cell Acute Lymphocytic
Leukemia
Damian J. Hussey,
Mario Nicola,
Sarah Moore,
Gregory B. Peters, and
Alexander Dobrovic
From the Department of Haematology-Oncology and University of
Adelaide Department of Medicine, The Queen Elizabeth Hospital,
Woodville, Australia; and the Division of Haematology, Institute of
Medical and Veterinary Science, Adelaide, Australia.
We determined the breakpoint genes of the translocation
t(4;11)(q21;p15) that occurred in a case of adult T-cell acute
lymphocytic leukemia (T-ALL). The chromosome 11 breakpoint was mapped
to the region between D11S470 and D11S860. The
nucleoporin 98 gene (NUP98), which is rearranged in several
acute myeloid leukemia translocations, is located within this region.
Analysis of somatic cell hybrids segregating the translocation
chromosomes showed that the chromosome 11 breakpoint occurs within
NUP98. The fusion partner of NUP98 was identified as the
RAP1GDS1 gene using 3' RACE. RAP1GDS1 codes for
smgGDS, a ubiquitously expressed guanine nucleotide exchange factor
that stimulates the conversion of the inactive GDP-bound form of
several ras family small GTPases to the active GTP-bound form. In the
NUP98-RAP1GDS1 fusion transcript (abbreviated as NRG), the 5' end of the NUP98 gene is joined in
frame to the coding region of the RAP1GDS1 gene. This
joins the FG repeat-rich region of NUP98 to RAP1GDS1,
which largely consists of tandem armadillo repeats. NRG fusion
transcripts were detected in the leukemic cells of 2 other adult T-ALL
patients. One of these patients had a variant translocation with a more
5' breakpoint in NUP98. This is the first report of an
NUP98 translocation in lymphocytic leukemia and the first time
that RAP1GDS1 has been implicated in any human malignancy.
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