Open AccessIdentification of SMURF1 as a possible target for 7q21.3‐22.1 amplification detected in a pancreatic cancer cell line by in‐house array‐based comparative genomic hybridization
Author(s) -
Suzuki Ayako,
Shibata Tatsuhiro,
Shimada Yutaka,
Murakami Yoshinori,
Horii Akira,
Shiratori Keiko,
Hirohashi Setsuo,
Inazawa Johji,
Imoto Issei
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00779.x
Subject(s) - comparative genomic hybridization , biology , gene duplication , copy number variation , gene , gene knockdown , fluorescence in situ hybridization , gene dosage , genetics , microbiology and biotechnology , ectopic expression , cancer research , gene expression , genome , computational biology , chromosome
Pancreatic cancer (PC) cell lines provide a useful starting point for the discovery and functional analysis of genes driving the genesis and progression of this lethal cancer. To increase our understanding of the gene copy number changes in pancreatic carcinomas and to identify key amplification and deletion targets, we applied genome‐wide array‐based comparative genomic hybridization using in‐house array (MCG Cancer Array‐800) to 24 PC cell lines. Overall, the analyses revealed high genomic complexity, with several copy number changes detected in each line. Homozygous deletions (log 2 ratio < –2) of eight genes (clones) were seen in 14 of the 24 cell lines, whereas high‐level amplifications (log 2 ratio > 2) of 10 genes (clones) were detected in seven lines. Among them, we focused on high‐level amplification at 7q22.1, because target genes for this alteration remain unknown. Through precise mapping of the altered region by fluorescence in situ hybridization, determination of the expression status of genes located within those regions, and functional analysis using knockdown of the gene expression or the ectopic overexpression approach in PC cell lines, as well as immunohistochemical analyses of candidates in primary tumors of PC, we successfully identified SMURF1 as having the greatest potential as a 7q21.3‐22.1 amplification target. SMURF1 may work as a growth‐promoting gene in PC through overexpression and might be a good candidate as a therapeutic target. Our results suggest that array‐based comparative genomic hybridization analysis combined with further genetic and functional examinations is a useful approach for identifying novel tumor‐associated genes involved in the pathogenesis of this lethal disease. ( Cancer Sci 2008; 99: 986–994)