Transvection Mediated by the Translocated Cyclin D1 Locus in Mantle Cell Lymphoma

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2008 Jul 16

PMID 18625744

Citations 17

Authors

Hui Liu

Jing Huang

Jin Wang

Shuguang Jiang

Alexis S Bailey

Devorah C Goldman

Markus Welcker

Victoria Bedell

Marilyn L Slovak

Bruce Clurman

Mathew Thayer

William H Fleming

Elliot Epner

Affiliations

Soon will be listed here.

Abstract

In mantle cell lymphoma (MCL) and some cases of multiple myeloma (MM), cyclin D1 expression is deregulated by chromosome translocations involving the immunoglobulin heavy chain (IgH) locus. To evaluate the mechanisms responsible, gene targeting was used to study long-distance gene regulation. Remarkably, these targeted cell lines lost the translocated chromosome (t(11;14)). In these MCL and MM cells, the nonrearranged cyclin D1 (CCND1) locus reverts from CpG hypomethylated to hypermethylated. Reintroduction of the translocated chromosome induced a loss of methylation at the unrearranged CCND1 locus, providing evidence of a transallelic regulatory effect. In these cell lines and primary MCL patient samples, the CCND1 loci are packaged in chromatin-containing CCCTC binding factor (CTCF) and nucleophosmin (NPM) at the nucleolus. We show that CTCF and NPM are bound at the IgH 3' regulatory elements only in the t(11;14) MCL cell lines. Furthermore, NPM short hairpin RNA produces a specific growth arrest in these cells. Our data demonstrate transvection in human cancer and suggest a functional role for CTCF and NPM.

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