Copy number alterations and expression profiles of candidate genes in a pulmonary inflammatory myofibroblastic tumor
Received 25 September 2009; received in revised form 8 January 2010; accepted 29 January 2010. published online 25 February 2010. Corrected Proof
Summary
Inflammatory myofibroblastic tumor (IMT) is a soft tissue neoplasm composed of myofibroblastic spindle cells accompanied by the inflammatory infiltrate. In addition to its phenotypic ambiguity, pathogenic mechanisms of the IMT also remain elusive. Although several chromosomal aberrations have been identified by karyotyping, detailed characteristics and extent of copy number alterations in IMT are unknown. Copy number alterations of an IMT case were examined using 30K whole-genome oligoarray-comparative genomic hybridization. RNA expression of putative cancer-related genes located in the chromosomal altered regions was assessed by qRT-PCR. We identified seven copy number gained regions, seven lost regions, nine amplifications and six homozygous deletions, which covers 2.5% of total genome. In homozygously deleted regions, RNA levels of putative tumor suppressors, SEMA3B, SEMA3F and SULT2A1, were significantly repressed being consistent with copy number status. In high-level amplification regions, RNA expression of four potential cancer-related genes was examined; GSTT1, ESR1, EVI1 and MITF. Among them, GSTT1 and ESR1 were significantly up-regulated, but EVI1 and MITF showed insignificant elevation of RNA expression. To our knowledge, this is the first genome-wide analysis of copy number alterations in IMT. Most of the putative cancer-related genes identified in this study are supposedly novel in IMT. Taken together, our results will help to elucidate the pathogenic mechanisms of IMT.
aIntegrated Research Center for Genome Polymorphism, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea
bDepartment of Microbiology, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea
cDepartment of Hospital Pathology, Seoul St.Mary's Hospital, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea
dDepartment of Pathology, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea
eDepartment of Pathology, Dankook University, College of Medicine, 29 Anseo-dong, Dongnam-gu, Cheonan-si, Chungnam 330-714, Republic of Korea
Corresponding author at: Department of Microbiology, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea. Tel.: +82 2 2258 7343; fax: +82 2 537 0572.