title: Genomic deletion and promoter methylation status of Hypermethylated in Cancer 1 (HIC1) in mantle cell lymphoma.
abstract: Mantle cell lymphomas (MCL), characterized by the t(11;14)(q13;q32), frequently carry secondary genetic alterations such as deletions in chromosome 17p involving the TP53 locus. Given that the association between TP53-deletions and concurrent mutations of the remaining allele is weak and based on our recent report that the Hypermethylated in Cancer 1 (HIC1) gene, that is located telomeric to the TP53 gene, may be targeted by deletions in 17p in diffuse large B-cell lymphoma (DLBCL), we investigated whether HIC1 inactivations might also occur in MCL. Monoallelic deletions of the TP53 locus were detected in 18 out of 59 MCL (31%), while overexpression of p53 protein occurred in only 8 out of 18 of these MCL (44%). In TP53-deleted MCL, the HIC1 gene locus was co-deleted in 11 out of 18 cases (61%). However, neither TP53 nor HIC1 deletions did affect survival of MCL patients. In most analyzed cases, no hypermethylation of the HIC1 exon 1A promoter was observed (17 out of 20, 85%). However, in MCL cell lines without HIC1-hypermethylation, the mRNA expression levels of HIC1 were nevertheless significantly reduced, when compared to reactive lymph node specimens, pointing to the occurrence of mechanisms other than epigenetic or genetic events for the inactivation of HIC1 in this entity.
authors: Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors: Heike
authors: H
authors: Stöcklein
authors: Grit
authors: G
authors: Hutter
authors: Jörg
authors: J
authors: Kalla
authors: Elena
authors: E
authors: Hartmann
authors: Yvonne
authors: Y
authors: Zimmermann
authors: Tiemo
authors: T
authors: Katzenberger
authors: Patrick
authors: P
authors: Adam
authors: Ellen
authors: E
authors: Leich
authors: Sylvia
authors: S
authors: Höller
authors: Hans Konrad
authors: HK
authors: Müller-Hermelink
authors: Andreas
authors: A
authors: Rosenwald
authors: German
authors: G
authors: Ott
authors: Martin
authors: M
authors: Dreyling