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The CD30 gene promoter microsatellite binds transcription factor Yin Yang 1 (YY1) and shows genetic instability in anaplastic large cell lymphoma
Author(s) -
Franchina M,
Woo AJ,
Dods J,
Karimi M,
Ho D,
Watanabe T,
Spagnolo DV,
Abraham LJ
Publication year - 2008
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2258
Subject(s) - anaplastic large cell lymphoma , cd30 , biology , microsatellite , microsatellite instability , cancer research , lymphoma , microbiology and biotechnology , gene , genetics , allele , immunology
CD30 is a member of the TNF receptor family. Our interest lies in understanding the control of CD30 expression, particularly as its over‐expression provides a diagnostic marker for a subset of non‐Hodgkin's lymphomas, particularly anaplastic large cell lymphoma (ALCL), and because anti‐CD30 treatment has been shown to be efficacious. We have identified a number of regulatory regions, including an Sp1 element in the minimal promoter, and a downstream promoter element that is required for start site selection. The discovery of both an activating AP1 site and an upstream microsatellite that represses transcriptional activity of CD30 suggests that this region is involved in dysregulation of CD30 expression. We have now identified the major microsatellite binding activity as transcription factor Yin Yang 1 by both one‐hybrid cDNA library screening and peptide mass fingerprinting. Due to the strong repressive effect of the microsatellite, we also investigated whether microsatellite instability may induce changes in CD30 expression and hence explain the over‐expression of CD30 in ALCL. Laser capture microdissection of ALCL biopsies and CD30 microsatellite typing indicated that the neoplastic cells show a high degree of variation, but this does not correlate with high CD30 expression seen in ALCL. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.