Overexpression through amplification of genes in chromosome region 17p11.2∼p12 in high-grade osteosarcoma

Maaike Van Dartel, Sandra Redeker, Johannes Bras, Marcel Kool, Theo J.M. Hulsebos

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34 Citations (Scopus)

Abstract

Osteosarcomas are malignant tumors of the bone that are characterized by complex genetic changes, including loss and amplification of chromosome regions. Region 17p11.2∼p12 is frequently found to be amplified in this tumor, suggesting the presence of an oncogene (or oncogenes) important in osteosarcoma tumorigenesis. We had previously determined amplification profiles for this region. Reasoning that amplification of a causative oncogene in a tumor should result in increased expression of that gene, we have now determined the expression status of genes and expressed sequence tags (ESTs) in 17p11.2∼p12. We constructed a 17p11.2∼p12-specific macroarray containing 40 genes and 21 ESTs from this region, which was used for expression profiling of 11 osteosarcoma samples (9 tumors and 2 cell lines) and of normal human osteoblasts. Compared to normal osteoblasts, genes with at least threefold increased expression were considered to be overexpressed in the tumor. Genes PMP22 and COPS3, EST AA126939 (encoding part of the hypothetical protein FLJ20343), and two anonymous ESTs (AA918483 and R02360) were found to be most consistently overexpressed after amplification. By real-time reverse transcriptase polymerase chain reaction, we could confirm the overexpression status of PMP22 and COPS3 but not of FLJ20343. We conclude that PMP22 and COPS3, and possibly also the three ESTs, are candidate amplification targets in 17p11.2∼p12 in osteosarcoma.

Original languageEnglish
Pages (from-to)8-14
Number of pages7
JournalCancer Genetics and Cytogenetics
Volume152
Issue number1
DOIs
Publication statusPublished - 1 Jul 2004
Externally publishedYes

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