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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2930-2936
MUC1 dysregulation as the consequence of a
t(1;14)(q21;q32) translocation in an extranodal lymphoma
Frédéric Gilles,
André Goy,
Yvonne Remache,
Peter Shue, and
Andrew D. Zelenetz
From the Laboratory of Molecular Hemato-Oncology, the Lymphoma
Service, and the Department of Medicine, Memorial Hospital, Memorial
Sloan-Kettering Cancer Center, New York, NY.
Cytogenetic abnormalities at chromosome 1q21 are among the most
common lesions in diffuse large-cell lymphoma and have been associated
with a poor prognosis. A novel cell line, SKI-DLCL-1, was established
from ascitic fluid that carries a t(1;14)(q21;q32) chromosomal
translocation. Using pulsed-field gel electrophoresis, the breakpoint
on the IgH locus mapped to a gamma locus between C 1 and C2. A cosmid library was prepared
from SKI-DLCL-1, and C -positive clones spanning the breakpoint were
identified by screening with fluorescence in situ hybridization. The
breakpoint occurs 860 bp downstream of the 3' UTR of the MUC1
gene. The break appears to be a staggered double-strand break
consistent with an error in immunoglobulin class switching. The MUC1
gene is highly transcribed and translated, and the protein is highly
glycosylated. It is postulated that MUC1 expression is brought under
the control of the 3'E enhancer. MUC1 lies in a region of
chromosome 1 characterized by an unusually high density of genes, with
7 known genes in a region of approximately 85 kb. To determine whether
there was a pleiotropic effect of the expression of genes in the region as a consequence of the translocation, the expression of 6 additional genes was assessed. None of the other genes in this region (CLK2, propin, COTE1, GBA, metaxin, and thrombospondin 3) are overexpressed in
SKI-DLCL-1. Thus, the translocation t(1;14)(q21;q32) seen in both the
primary tumor and the derived cell line results in the marked
overexpression of MUC1 without affecting the expression of other genes
in the region.
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