𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Silencing of the UCHL1 gene in giant cell tumors of bone

✍ Scribed by Jörg Fellenberg; Burkhard Lehner; Daniela Witte

Publisher
John Wiley and Sons
Year
2010
Tongue
French
Weight
852 KB
Volume
127
Category
Article
ISSN
0020-7136

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Giant cell tumors are heterogeneous tumors consisting of multinucleated giant cells, fibroblast‐like stromal cells and mononuclear histiocytes. The stromal cells have been identified as the neoplastic cell population, which promotes the recruitment of histiocytes and the formation of giant cells. Strong evidence exists that these cells develop from mesenchymal stem cells (MSCs) but little is known about the molecular mechanisms involved in GCT tumorigenesis. The aim of our study was the identification of cancer‐related genes differentially expressed in GCTs compared to MSCs in order to identify possible targets for aberrant promoter methylation, which may contribute to MSC transformation and GCT development. Gene expression of 440 cancer‐related genes was analyzed by DNA microarrays in GCT stromal cells and bone marrow‐derived MSCs (BMSCs) isolated from the same patient (n = 3) to avoid interindividual variations. Differential expression was identified for 14 genes, which could be confirmed by quantitative PCR in further 21 GCT and 10 BMSC samples. The most pronounced difference in gene expression was detected for UCHL1, an important regulator of the ubiquitin proteasome pathway. Methylation‐specific PCR and bisulfite sequencing revealed a strong methylation of the CpG island covering the UCHL1 promoter in GCT stromal cells, whereas methylation was completely absent in BMSCs. UCHL1 expression in stromal cells could be restored by the methylation inhibitor 5‐aza‐dC. These data demonstrate that the UCHL1 gene is inactivated in GCTs but not in MSCs, suggesting a possible role of UCHL1 in MSC transformation and GCT development.

📜 SIMILAR VOLUMES

Silencing of the UCHL1 gene in human col
Silencing of the UCHL1 gene in human colorectal and ovarian cancers
✍ Eriko Okochi-Takada; Kazuyuki Nakazawa; Mika Wakabayashi; Akiko Mori; Shizue Ich 📂 Article 📅 2006 🏛 John Wiley and Sons 🌐 French ⚖ 599 KB

## Abstract Aberrant DNA methylation is associated with many types of human cancers. To identify genes silenced in human colorectal cancers, we performed a microarray analysis for genes whose expression was induced by treatment of HCT116 human colon cancer cells with a demethylating agent, 5‐aza‐2′

Malignancy in giant cell tumor of bone
Malignancy in giant cell tumor of bone
✍ Franco Bertoni; Patrizia Bacchini; Eric L. Staals 📂 Article 📅 2003 🏛 John Wiley and Sons 🌐 English ⚖ 1023 KB

## Abstract ## BACKGROUND The term __malignant giant cell tumor__ embraces multiple entities and therefore can be confusing. The goals of the current study were to define the clinicopathologic and histologic features of malignancy in giant cell tumors and to clarify the terminology. ## METHODS T

No EWS/FLI1 fusion transcripts in giant-
No EWS/FLI1 fusion transcripts in giant-cell tumors of bone
✍ Ioannis Panagopoulos; Fredrik Mertens; Henryk A. Domanski; Margareth Isaksson; O 📂 Article 📅 2001 🏛 John Wiley and Sons 🌐 French ⚖ 104 KB 👁 1 views

Giant-cell tumor of bone (GCT) is a locally aggressive neoplasm of unknown etiology and pathogenesis. Cytogenetically, no consistent chromosomal alterations, apart from telomeric associations involving various chromosome ends, have been described. Recently, however, it was reported that by using hig

Giant cell tumor of the bones of the han
Giant cell tumor of the bones of the hand and foot
✍ Roberto Biscaglia; Patrizia Bacchini; Franco Bertoni 📂 Article 📅 2000 🏛 John Wiley and Sons 🌐 English ⚖ 945 KB

## BACKGROUND. Giant cell tumor of the small bones of the hand and foot is suspected of having some peculiar features compared with giant cell tumor in other sites. Moreover, it could share some features with other giant cell rich lesions involving the hand and foot, and this may affect the differe