MUC1 dysregulation as the consequence of a t(1;14)(q21;q32) translocation in an extranodal lymphoma

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.