Isolation of novel genes within the amplified regions in tumors detected by comparative genomic hybridization (CGH).
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概要
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Comparative genomic hybridization (CGH) is a powerful technique to identify novel amplification sites through all human chromosomes. We employed CGH to explore genomic imbalances in 19 malignant fibrous histiocytomas (MFHs). Together with losses and gains in various chromosome regions, distinct high-level amplifications were found in six loci (4q12-21, 8p21-pter, 8q24.1-qter, 9p12-13, 12p11.2-pter, and 15q11.2-15), suggesting that those regions may contain unknown genes responsible for carcinogenesis. We focused on the 8p amplicon, and a novel gene designated MASL1 (MFH-amplified sequences with leucine-rich repeats 1) was isolated from within this narrowly defined region. Expression of the MASL1 gene was enchanced significantly in MFH tumors bearing the 8p amplicon. The primary structure of its deduced product revealed an ATP/GTP-binding site, three leucine zipper domains, and a leucine-rich tandem repeat, all of which are important structural or functional elements for interactions among proteins related to the cell cycle. These features suggest that overexpression of MASL1 might well be oncogenic with respect to MFH.
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