In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 3400-3400
Abstract:
Osteosarcomas are copy-number alteration (CNA)-rich malignant bone tumors. Using microarrays, fluorescence in-situ hybridization and quantitative polymerase chain reaction we characterize a focal region of chr3q13.31 (osteo3q13.31) harboring CNAs in 80% of osteosarcomas. As such, osteo3q13.31 is the most altered region in osteosarcoma and contests the view that CNAs in osteosarcoma are non-recurrent. Most (67%) osteo3q13.31 CNAs are deletions, 75% of which are mono-allelic, and are frequently accompanied by loss-of-heterozygosity (LOH) in flanking DNA. These CNAs often involve the non-coding RNAs (ncRNAs) LOC285194 and BC040587, and sometimes, the limbic system-associated membrane protein (LSAMP) tumor suppressor (TS). Change in expression of osteo3q13.31 genes is ubiquitous in osteosarcoma, usually involving loss of expression. Underscoring the functional significance of osteo3q13.31 CNAs, expression of LOC285194 and BC040587 and sometimes LSAMP, correlates with the presence of osteo3q13.31 CNAs. Focal osteo3q13.31 CNAs and LOH are also common in cell lines from other cancers, identifying osteo3q13.31 as a universal candidate TS region. Osteo3q13.31 genes may function as a unit, since we demonstrate significant correlation between the expression of distantly spaced LSAMP, LOC285194, and BC040587. Supporting this notion, depletion of either LSAMP or LOC285194 promotes proliferation of normal osteoblasts through regulation of apoptotic and cell cycle transcripts, and vascular endothelial growth factor (VEGF)/VEGF receptor 1 (VEGFR1). Furthermore, the presence of LOC285194 or BC040587 deletions in tumor DNA is associated with poor survival of osteosarcoma patients. Osteo3q13.31 therefore represents a novel universal TS region containing several cooperatively acting genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3400.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-3400
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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