F. Gilles et al., MUC1 dysregulation as the consequence of a t(1;14)(q21;q32) translocation in an extranodal lymphoma, BLOOD, 95(9), 2000, pp. 2930-2936
Cytogenetic abnormalities at chromosome 1q21 are among the most common lesi
ons in diffuse large cell lymphoma and have been associated with a poor pro
gnosis. A novel cell line, SKI-DLCL-1, was established from ascitic fluid t
hat carries a t(1;14)(q21;q32) chromosomal translocation. Using pulsed-fiel
d gel electrophoresis, the breakpoint on the IgH locus mapped to a gamma lo
cus between C alpha(1) and C alpha(2). A cosmid library was prepared from S
KI-DLCL-1, and C gamma-positive clones spanning the breakpoint were identif
ied by screening with fluorescence in situ hybridization. The break-point o
ccurs 860 bp downstream of the 3' UTR of the MUC1 gene. The break appears t
o be a staggered double-strand break consistent with an error in immunoglob
ulin class switching. The MUC1 gene is highly transcribed and translated, a
nd the protein is highly glycosylated. It is postulated that MUC1 expressio
n is brought under the control of the 3'E alpha enhancer. MUC1 lies in a re
gion of chromosome 1 characterized by an unusually high density of genes, w
ith 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 wa
s assessed. None of the other genes in this region (CLK2, propin, COTE1, GB
A, metaxin, and thrombospondin 3) are overexpressed in SKI-DLC-1, Thus, the
translocation t(1;14)(q21;q32) seen in both the primary tumor and the deri
ved cell line results in the marked overexpression of MUC1 without affectin
g the expression of other genes in the region. (Blood, 2000;95:2930-2936) (
C) 2000 by The American Society of Hematology.