LSAMP, a novel candidate tumor suppressor gene in human osteosarcomas, identified by array comparative genomic hybridization
- 13 May 2009
- journal article
- research article
- Published by Wiley in Genes, Chromosomes and Cancer
- Vol. 48 (8), 679-693
- https://doi.org/10.1002/gcc.20675
Abstract
Osteosarcomas are the most common primary malignant tumor of bone, and almost all conventional osteosarcomas are high-grade tumors with complex karyotypes. We have examined DNA copy number changes in 36 osteosarcoma tumors and 20 cell lines using microarray-based comparative genomic hybridization. The most frequent minimal recurrent regions of gain identified in the tumor samples were in 1q21.2-q21.3 (78% of the samples), 1q21.3-q22 (78%), and 8q22.1 (72%). Minimal recurrent regions in 10q22.1-q22.2 (81%), 6q16.1 (67%), 13q14.2 (67%), and 13q21.1 (67%) were most frequently lost. A small region in 3q13.31 (2.1 Mb) containing the gene limbic system-associated membrane protein (LSAMP) was frequently deleted (56%). LSAMP has previously been reported to be a candidate tumor suppressor gene in other cancer types. The deletion was validated using fluorescence in situ hybridization, and the expression level and promoter methylation status of LSAMP were investigated using quantitative real-time reverse transcription PCR and methylation-specific PCR, respectively. LSAMP showed low expression compared to two normal bone samples in 6/15 tumors and 5/9 cell lines with deletion of 3q13.31, and also in 5/14 tumors and 3/11 cell lines with normal copy number or gain. Partial or full methylation of the investigated CpG island was identified in 3/30 tumors and 7/20 cell lines. Statistical analyses revealed that loss of 11p15.4-p15.3 and low expression of LSAMP (both P = 0.011) were significantly associated with poor survival. Our results show that LSAMP is a novel candidate tumor suppressor gene in osteosarcomas.Keywords
This publication has 39 references indexed in Scilit:
- Comparative genomic hybridization analysis of abnormalities in chromosome 21 in childhood osteosarcomaCancer Genetics and Cytogenetics, 2007
- Comparison of gene expression profiles between primary tumor and metastatic lesions in gastric cancer patients using laser microdissection and cDNA microarrayWorld Journal of Gastroenterology, 2006
- Management of high-grade bone sarcomas over two decades: The Norwegian Radium Hospital experienceActa Oncologica, 2006
- Role of insulin-like growth factor 1 receptor signalling in cancerBritish Journal of Cancer, 2005
- Gene amplifications in osteosarcoma-CGH microarray analysisGenes, Chromosomes and Cancer, 2004
- Frequent amplification and rearrangement of chromosomal bands 6p12‐p21 and 17p11.2 in osteosarcomaGenes, Chromosomes and Cancer, 2003
- Amplification and overexpression of COPS3 in osteosarcomas potentially target TP53 for proteasome-mediated degradationOncogene, 2003
- Neurotrimin Mediates Bifunctional Effects on Neurite Outgrowth via Homophilic and Heterophilic InteractionsJournal of Neuroscience, 1998
- Comparative genomic hybridization analysis of human sarcomas: II. Identification of novel amplicons at 6p and 17p in osteosarcomasGenes, Chromosomes and Cancer, 1995
- Comparative genomic hybridization analysis of human sarcomas: I. Occurrence of genomic imbalances and identification of a novel major amplicon at 1q21–q22 in soft tissue sarcomasGenes, Chromosomes and Cancer, 1995