Identification of a novel gene, MASL1, within an amplicon at 8p23.1 detected in malignant fibrous histiocytomas by comparative genomic hybridization.
We used comparative genomic hybridization to study malignant fibrous histiocytomas (MFHs) from 19 patients to detect changes in the copy number of DNA sequences, along entire chromosomes. Together with losses and gains in various chromosomal regions, distinct high-level amplifications were found at six loci (4q12-21, 8p21-pter, 8q24.1-qter, 9q12-13, 12p11.2-pter, and 15q11.2-15), suggesting that those regions may contain unknown (proto) oncogenes. We focused on the 8p amplicon, where detailed characterization allowed us to determine that the minimal common amplified region lay between markers D8S1819 and D8S550 at 8p23.1. A novel gene designated MASL1 (MFH-amplified sequences with leucine-rich tandem repeats 1) was isolated from within this narrowly defined region. Expression of the MASL1 gene was enhanced 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.
Sakabe
T
T
Laboratory of Genome Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Japan.
Shinomiya
T
T
Mori
T
T
Ariyama
Y
Y
Fukuda
Y
Y
Fujiwara
T
T
Nakamura
Y
Y
Inazawa
J
J
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015139:Blotting, Southern; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D002869:Chromosome Aberrations; D002898:Chromosomes, Human, Pair 8; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015513:Oncogene Proteins; D009857:Oncogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction