%0 Journal Article
%T Mapping and characterization of the amplicon near APOA2 in 1q23 in human sarcomas by FISH and array CGH
%A Stine H Kresse
%A Jeanne-Marie Berner
%A Leonardo A Meza-Zepeda
%A Simon G Gregory
%A Wen-Lin Kuo
%A Joe W Gray
%A Anne Forus
%A Ola Myklebost
%J Molecular Cancer
%D 2005
%I BioMed Central
%R 10.1186/1476-4598-4-39
%X We have used fluorescence in situ hybridisation (FISH) and microarray-based comparative genomic hybridisation (array CGH) to map and define the borders of the amplicon in 10 sarcomas. A subregion of approximately 800 kb was identified as the core of the amplicon. The amplification patterns of nine possible candidate target genes located to this subregion were determined by Southern blot analysis. The genes activating transcription factor 6 (ATF6) and dual specificity phosphatase 12 (DUSP12) showed the highest level of amplification, and they were also shown to be over-expressed by quantitative real-time reverse transcription PCR (RT-PCR). In general, the level of expression reflected the level of amplification in the different tumours. DUSP12 was expressed significantly higher than ATF6 in a subset of the tumours. In addition, two genes known to be transcriptionally activated by ATF6, glucose-regulated protein 78 kDa and -94 kDa (GRP78 and GRP94), were shown to be over-expressed in the tumours that showed over-expression of ATF6.ATF6 and DUSP12 seem to be the most likely candidate target genes for the 1q23 amplification in sarcomas. Both genes have possible roles in promoting cell growth, which makes them interesting candidate targets.Gains or amplification of the long arm of chromosome 1 is among the most common chromosomal abnormalities in human neoplasia [1]. Local gains or high-level amplification affecting 1q21-q23 is particularly frequent, and was first described for sarcomas [2-4]. Sarcomas are a heterogeneous group of malignant tumours of various supporting- and connective tissues, ranging from the almost benign well-differentiated liposarcomas (WDLS) to aggressive tumour forms, such as fibrosarcomas, osteosarcomas and malignant fibrous histiocytomas (MFH) [5]. Although infrequent, these tumours have been widely studied at the molecular level, and this has provided insight into mechanisms of importance for tumour development in general. Notably, amplificatio
%U http://www.molecular-cancer.com/content/4/1/39